Table of Contents
Overview
Definition of Toxicology
Toxicology is defined as the science of poisons, encompassing the study of the adverse effects of chemicals or physical agents on living organisms, including humans, animals, and plants.[3.1] This interdisciplinary field integrates knowledge from various scientific domains, such as biology, chemistry, and physics, as well as their respective subspecialties, including genetics, analytical chemistry, and pharmacology.[3.1] The scope of toxicology is broad, as it overlaps with numerous disciplines, allowing for a comprehensive understanding of how different substances can cause harm.[3.1] Within toxicology, there are specialized areas, such as forensic toxicology, which applies toxicological principles to legal and medical investigations of death, poisoning, and drug use.[4.1] Clinical toxicology focuses on the diagnosis and treatment of poisoning, evaluating detection methods and the mechanisms of action of toxic substances in both humans and animals.[5.1] Toxicology is an interdisciplinary science that focuses on the study of poisons and their effects on living organisms, integrating knowledge from various fields such as biology, chemistry, pharmacology, and pathology.[1.1] A fundamental concept in toxicology is the dose-response relationship, which correlates the level of exposure to a toxic agent with changes in health or body functions; generally, higher doses result in more severe responses.[36.1] This relationship is crucial for understanding how different doses of a chemical can lead to varying effects, often referred to as a "graded" response, where the measured effect is continuous over a range of doses.[37.1] Understanding the mechanisms of toxicity is essential, as it provides a rational basis for interpreting toxicity data, estimating the likelihood of harmful effects, and designing less hazardous drugs and industrial chemicals.[35.1] Additionally, knowledge of these mechanisms aids in establishing procedures to prevent or counteract toxic effects, which is particularly important in clinical toxicology where the timely use of antidotes can stabilize patients following exposure to known poisons.[15.1]Importance in Public Health
Understanding patient history is a fundamental aspect of toxicology that significantly impacts public health. A comprehensive patient history is crucial for diagnosing and managing cases of poisoning or exposure to toxic substances, as it aids in identifying the offending agent and determining the appropriate course of action.[38.1] It is essential for clinicians to take an exposure history for every patient, particularly when the patient's illness occurs at an atypical age or is unresponsive to treatment.[39.1] This history-taking process is vital because many organ systems can be affected by toxic exposure, and the latency period from exposure to the manifestation of disease can vary widely.[39.1] In cases of acute poisoning, the assessment of the patient includes not only history-taking but also evaluating airway, breathing, circulation, and consciousness level, along with physical examinations to elicit relevant clinical signs and appropriate investigations.[40.1] Diagnosis typically relies on the patient's history, recognition of toxidromes when present, and the results of investigations.[40.1] In situations where patients are unconscious, obtaining a history from friends or relatives can be invaluable, and diagnosis may often be inferred from available evidence, such as medication containers or notes.[41.1] Furthermore, self-poisoning must always be considered in the differential diagnosis for any patient presenting with altered consciousness.[41.1] The intersection of toxicology and public health is further emphasized by the evolving challenges posed by emerging contaminants, such as microplastics and pharmaceuticals. These contaminants can enter the human body through various pathways, leading to significant health hazards, including cell injury and hormone disruption.[26.1] The role of toxicology in addressing these emerging threats is critical, as it requires a systems-level approach that incorporates environmental science, epidemiology, and toxicology to capture the full spectrum of climate-related toxicological risks.[24.1] As such, adaptive regulatory frameworks that can respond rapidly to these emerging threats are necessary for effective public health protection.[24.1]History
Ancient Practices and Knowledge
Toxicology has its roots in ancient practices where early humans utilized their understanding of plant and animal toxins for survival and warfare. The term "toxicology" itself is derived from the Greek word for poison (toxicon) and the study of science (logos), with its formalization occurring in the 17th century, although the empirical practices associated with it date back to antiquity.[44.1] Ancient civilizations, such as the Egyptians, Persians, and Chinese, recognized the dual nature of plants, using them for both beneficial and harmful purposes. For instance, the Egyptians employed toxic plants like Aconite to coat arrowheads, ensuring that their enemies would suffer a slow and painful demise.[72.1] In these early societies, knowledge of toxic substances was crucial for survival. People learned to distinguish between safe and hazardous substances, which laid the groundwork for modern toxicology.[46.1] The ancient herbalists effectively utilized plants in ways that maximized their medicinal benefits while minimizing risks, demonstrating an early understanding of the therapeutic and toxic properties of substances.[64.1] This understanding was encapsulated in Paracelsus's assertion that there is no non-toxic substance, emphasizing the importance of dosage in determining a substance's effects.[48.1] The documentation of toxicological knowledge can be traced back to ancient texts, such as the Ebers and Edwin Smith Papyri, which detail the use of various toxins and their classifications.[47.1] Furthermore, hunter-gatherer societies, such as the Yanomami of the Amazon, have historically employed poisons derived from local plants to enhance their hunting techniques, showcasing a practical application of toxicological knowledge.[62.1]Development of Modern Toxicology
The development of modern toxicology has undergone significant transformation from its historical origins, evolving from anecdotal practices to a more systematic and empirical science. The term "toxicology," which is derived from the Greek words for poison (toxicon) and scientific study (logos), was coined in the 17th century, marking a crucial point in the field's evolution.[65.1] Initially, toxicology was an empirical science, and it did not transition into a more quantitative discipline until the emergence of chemistry and analytical science.[65.1] This shift allowed for a more organized collection and arrangement of various animal, plant, and mineral materials believed to possess healing properties, which were subsequently published in erudite Latin editions under the sponsorship of elite medical organizations.[66.1] By the early 20th century, toxicology was still in its infancy, with no established specialty, poison control centers, or comprehensive understanding of household and occupational toxic hazards in the United States.[50.1] This period was marked by a lack of oversight in pharmaceutical manufacturing and drug labeling, highlighting the need for improved public health measures and regulatory frameworks.[50.1] As the understanding of chemical safety evolved, ethical considerations surrounding the use of poisons and toxic substances became increasingly prominent, influencing modern regulations and public perceptions.[52.1] Advancements in analytical methods have significantly transformed toxicological research, enabling a more comprehensive understanding of toxic substances compared to earlier empirical observations. Recent developments encompass a diverse range of analytical techniques, including mass spectrometry and its integration with chromatography and capillary electrophoresis, which enhance the detection and quantification of toxic substances in various environments.[54.1] High-resolution mass spectrometry (HRMS) offers superior mass resolution and accuracy, allowing toxicologists to detect and identify a broader range of analytes with enhanced sensitivity and selectivity.[58.1] Furthermore, analytical chemistry plays a crucial role in chemical toxicology research by facilitating the determination of the dose or concentration of test chemicals, as well as characterizing metabolites and detecting molecular interactions.[59.1] These advancements collectively empower toxicologists to address emerging challenges in environmental assessment and improve risk assessment methodologies. The recent advancements in computational toxicology and artificial intelligence have significantly transformed the methods used to evaluate toxic effects on human health and the environment. Increased efforts in these areas have led to innovative testing methods that are central to contemporary toxicological research.[67.1] In the current era characterized by big data, the concepts of volume, velocity, and variety have become essential in understanding the vast amounts of data available for analysis.[68.1] This shift towards utilizing big data and advanced computational techniques marks a pivotal change from traditional empirical observations to more sophisticated and predictive models in toxicological assessments.[67.1]Recent Advancements
Innovative Technologies in Toxicology Research
Recent advancements in toxicology research have been significantly influenced by innovative technologies that enhance the understanding and prediction of chemical toxicity. One of the most notable developments is the integration of artificial intelligence (AI) into toxicology, which has transformed the field from a primarily observational science to a data-rich discipline. This shift allows for the application of machine learning algorithms and deep learning architectures to predict various toxicity properties and assess safety endpoints effectively.[84.1] In vitro testing methods, including organ-on-a-chip technologies and advanced imaging systems, have emerged as critical tools in modern toxicology. These methods facilitate the study of toxicity mechanisms and improve the translatability of findings to human health, thereby supporting the development of safety biomarkers and the mitigation of side effects.[85.1] Additionally, model organisms such as C. elegans, Danio rerio, and Drosophila melanogaster are increasingly utilized to provide insights into toxicological responses, further enhancing the predictive capabilities of toxicology research.[82.1] Computational toxicology has also gained prominence, utilizing machine learning and deep learning techniques to evaluate chemical toxicity more efficiently than traditional animal models, which are often costly and time-consuming.[89.1] This approach not only streamlines the drug discovery process but also helps identify compounds with the greatest potential for safe and effective use in humans, thereby reducing the risk of late-stage failures in drug development.[88.1] The integration of new testing systems and "omics" technologies presents significant challenges for regulatory toxicology, as it raises critical questions about their applicability for regulatory purposes.[90.1] These methodologies, while promising, have led to hesitance among relevant stakeholders regarding their implementation in a broader context.[91.1] Collaborative efforts between researchers, industries, and regulatory bodies are essential to develop standardized protocols and validation frameworks that will streamline the regulatory approval process for in vitro and in silico methods, as well as invertebrate models.[94.1] Such initiatives are crucial for facilitating the incorporation of these innovative methodologies into standard toxicological assessments.Key Concepts In Toxicology
Dose-Response Relationship
The dose-response relationship is a fundamental concept in toxicology that correlates the level of exposure to a substance with changes in body functions or health outcomes. Generally, it is observed that as the dose increases, the severity of the response also escalates, indicating a direct relationship between exposure and adverse health effects.[36.1] This relationship is based on observed data from experimental animal, human clinical, or cell studies, which helps toxicologists determine the threshold dose at which toxic effects first occur.[156.1] The dose-response curve serves as a visual representation of the response rates of a population to a range of doses of a substance, typically exhibiting an "S" shape.[156.1] This curve is crucial for toxicologists as it aids in assessing what percentage of individuals may experience harm at specific doses, thereby informing risk assessment and safety evaluations.[157.1] The evaluation of toxicity is a critical component of health risk assessment, which encompasses two primary steps: hazard identification and dose-response evaluation.[154.1] Hazard identification involves detailing the specific forms of toxicity that a chemical may induce, such as neurotoxicity and carcinogenicity.[154.1] Following this, dose-response evaluation is essential for understanding the relationship between the dose of a chemical and the extent of its toxic effects. This relationship is typically represented by a dose-response curve, which visually illustrates the response rates of a population to varying doses of a substance and often exhibits an "S" shape.[156.1] Furthermore, knowledge of the dose-response relationship is vital for determining the threshold dose, defined as the minimum amount of a substance that produces a detectable effect.[156.1] In practical applications, the dose-response relationship aids toxicologists in predicting the percentage of individuals who may experience harmful effects at various exposure levels. For instance, in the case of alcohol consumption, toxicologists utilize dose-response curves to ascertain the doses that could lead to adverse health effects, thereby informing guidelines for safe consumption.[157.1] Overall, the dose-response relationship serves as a vital tool in risk assessment, enabling the evaluation of potential health risks associated with chemical exposures and guiding public health interventions.Exposure Pathways and Susceptibility Factors
Exposure pathways in toxicology refer to the routes through which toxic substances enter the body, significantly influencing the potential for adverse health effects. These pathways include inhalation, ingestion, and dermal contact, each presenting unique risks and symptoms associated with acute toxicity. For instance, inhalation of toxicants can lead to respiratory symptoms, while skin contact may result in lesions, and ingestion often mimics acute gastrointestinal distress.[143.1] The severity of symptoms can vary based on the exposure route, the amount of substance involved, and the duration of exposure.[144.1] Susceptibility factors play a crucial role in determining an individual's response to toxic substances. Biological factors such as age, sex, genetic predisposition, and overall health can influence how a person metabolizes and reacts to toxins. For example, individuals with pre-existing conditions like liver or renal disease may experience heightened toxicity due to impaired biotransformation and excretion processes.[160.1] Additionally, idiosyncratic responses, which are unpredictable and may stem from genetic factors or immune system status, can complicate the assessment of toxicity and treatment protocols.[159.1] Understanding these exposure pathways and susceptibility factors is essential for developing effective risk assessment strategies and management plans in toxicology. Regulatory toxicologists, for instance, focus on establishing safe levels of chemical exposure to protect public health, taking into account these variables to mitigate risks associated with toxic substances.[139.1]In this section:
Health OutcomesHealth EffectsSafety EvaluationsHealth Risk AssessmentPublic Health Interventions
Applications Of Toxicology
Toxicology in Drug Development
Toxicology plays a crucial role in drug development, particularly within the fields of veterinary pharmacology and toxicology. These disciplines are integral to the creation of new compounds, including antibiotics and antiparasitics, which are essential for controlling infectious diseases in animals. The development of analgesics and non-steroidal anti-inflammatory drugs also falls under this umbrella, highlighting the importance of toxicological assessments in ensuring the safety and efficacy of new medications for various animal species.[197.1] The integration of veterinary toxicology with pharmacology is particularly significant as it addresses the complexities associated with different animal species, breeds, ages, and physiological statuses. These factors can influence how animals respond to drugs, food, feed, pesticides, and other toxic substances.[197.1] As such, toxicological evaluations are critical in identifying potential adverse effects and ensuring that new drugs are both safe and effective for their intended use. Veterinary pharmacology and toxicology are increasingly recognized as essential disciplines within the "One Health" paradigm, which emphasizes the interconnectedness of human, animal, and environmental health. These fields contribute to reducing risks within the animal-human ecosystem, particularly through the responsible use of antibiotics, which is vital for maintaining safety and health in the animal husbandry industry.[198.1] Furthermore, Green Veterinary Pharmacology and Toxicology represents a sustainable approach aimed at minimizing the use of chemicals, thereby addressing issues such as drug resistance and the persistence of chemical residues in the environment.[195.1] This integrated perspective not only enhances our understanding of toxic exposures but also improves treatment outcomes for affected animals, aligning with the broader goals of public health and environmental sustainability.Environmental Toxicology and Public Policy
Environmental toxicology is integral to the development of public policy aimed at protecting human health and the environment. By identifying and analyzing toxic chemicals, toxicology studies help assess potential health hazards and mitigate adverse effects from exposure to these substances.[178.1] The Public Health Toxicology Program addresses health concerns from chemical or biological agents, offering assessments and recommendations to reduce health risks.[179.1] In the United States, agencies like the Environmental Protection Agency (EPA), Food and Drug Administration (FDA), Occupational Safety and Health Administration (OSHA), and Consumer Product Safety Commission (CPSC) establish regulations to protect against health effects from various substances.[191.1] The Food Quality Protection Act (FQPA) of 1996 is a notable example of how toxicological findings can drive regulatory changes to ensure food safety.[192.1] The Agency for Toxic Substances and Disease Registry (ATSDR) develops toxicological profiles for chemicals at hazardous waste sites, providing evaluations that guide public health decisions and regulatory actions.[193.1] The precautionary principle, increasingly adopted by public health advocates, influences legal frameworks and international treaties, particularly in environmental and food safety contexts.[194.1] Environmental pollution from toxic pollutants threatens ecosystems and human health, infiltrating air, water, and soil, and causing biodiversity loss and damage to natural resources.[199.1] Contamination can lead to health issues and fatalities among wildlife, highlighting the need for effective environmental protection policies.[200.1] The overuse of agrochemicals has been linked to biodiversity declines, emphasizing the importance of informed policy-making.[202.1] Prioritizing chemical exposures for public health studies requires focusing on adverse health outcomes through multiple data streams, rather than individual chemicals.[207.1] This is crucial for communities near industrial activities, where evidence suggests increased exposure to hazardous pollutants and health effects.[208.1] The rise in industrial chemical production leads to widespread population exposures and significant health impacts.[210.1] Low-wealth communities and communities of color often face disproportionate exposure and health impacts, exacerbated by regulatory delays.[210.1] Understanding these dynamics is essential for informing public health policies and developing effective regulations to protect human health and the environment.In this section:
Challenges In Toxicology
Addressing Chemical Mixtures
Toxicologists face significant challenges in addressing the effects of chemical mixtures, which are increasingly prevalent due to the rising use of chemicals in various products and industries. One of the primary difficulties is the identification and assessment of the combined effects of multiple chemicals, as traditional toxicological studies often focus on single substances rather than complex mixtures.[250.1] This limitation complicates risk assessment and regulatory decision-making, as the interactions between chemicals can lead to unexpected toxicological outcomes. Moreover, the advent of new testing systems and "omics"-technologies has introduced additional complexities. These advanced methods have the potential to enhance the understanding of mixture toxicity, yet they also raise questions regarding their applicability for regulatory purposes.[247.1] The challenge lies in determining how these innovative approaches can be integrated into existing regulatory frameworks to effectively address the nuances of chemical mixtures. Globalization further complicates the situation, as regulatory standards vary significantly across jurisdictions. This disparity necessitates harmonization efforts to facilitate international trade while ensuring safety.[246.1] However, achieving full harmonization remains a challenge due to differing regulatory requirements and the dynamic nature of legislation, which evolves to keep pace with societal and technological changes.[252.1]Ethical Considerations in Toxicology Research
Ethical considerations in toxicology research are critical, particularly due to the significant challenges faced by the field. Toxicologists encounter substantial difficulties stemming from limited funding for research and testing, which can impede their ability to conduct thorough studies necessary for ensuring public health and safety.[211.1] Furthermore, funding allocation in toxicology is often influenced by the priorities of the funding bodies, such as governmental agencies, which may focus on research that addresses pressing public health concerns, including the safety of consumer products and the impact of pollutants.[233.1] This dynamic can create gaps in research areas that are vital for public health, as the interests of funding bodies may not always align with the most urgent needs in toxicology. Toxicology is currently encountering significant challenges that affect the development of new regulatory guidance, public health protection, and research directions. These challenges are particularly pronounced in the context of nanomaterials, where the assessment of risks is complicated by the existence of numerous nanoforms, discordant data, and conflicting results found in the literature. Furthermore, specific difficulties arise in the application of strategies such as grouping and read-across, which underscores the necessity for New Approach Methodologies (NAMs) to support Next Generation Risk Assessment (NGRA).[221.1] As toxicology grapples with these complexities, it is essential to address the associated risks and reduce uncertainties to effectively navigate the evolving landscape of regulatory mandates and research programs.[212.1] Effective communication of toxicological findings is another ethical consideration. Toxicologists face the challenge of conveying complex scientific information to the public in a manner that is both understandable and transparent. This is crucial for fostering trust and informed decision-making among communities.[225.1] Public health communication strategies must embrace an ecological perspective, tailoring messages to different audiences to bridge the gap between scientific findings and community understanding.[226.1] The field of toxicology currently faces significant data analysis challenges, particularly in the context of large and high-dimensional datasets.[235.1] There is a pressing need to improve the analysis of these datasets, as well as to better advise and train "wet lab" scientists in their utilization.[235.1] Addressing these issues is crucial for enhancing the quality of toxicological research and ensuring that findings are effectively integrated into public health initiatives. Furthermore, discussions between wet lab and dry lab scientists highlight the importance of developing methods for organizing and analyzing high-dimensional data, which is essential for advancing the field.[235.1] The application of supervised machine learning methods has been identified as a valuable approach for incorporating such data into toxicological studies.[235.1]In this section:
References
[1] What is Toxicology? - Toxicology Education Foundation — Toxicology is an interdisciplinary science, integrating information from biology and virtually all of its subspecialties (e.g., genetics, endocrinology and molecular biology) as well as math, physics and chemistry and its subspecialties (e.g. analytical, organic, and clinical chemistry).
[3] Toxicology | Poisons, Effects on Living Systems, Biochemistry ... — Toxicology, study of poisons and their effects, particularly on living systems. Because many substances are known to be poisonous to life (whether plant, animal, or microbial), toxicology is a broad field, overlapping with biochemistry, histology, pharmacology, pathology, and many other disciplines.
[4] Toxicology - Wikipedia — Forensic toxicology is the discipline that makes use of toxicology and other disciplines such as analytical chemistry, pharmacology and clinical chemistry to aid medical or legal investigation of death, poisoning, and drug use.
[5] PDF — Clinical Toxicology: Diagnosis and treatment of poisoning; evaluation of methods of detection and intoxication, mechanism of action in humans (human tox, pharmaceutical tox) and animals (veterinary tox).
[15] An approach to the management of acute poisoning in emergency settings ... — The availability of sophisticated antidotes and their use have become essential in clinical toxicology. In most cases, an initial use of an antidote is recommended for stabilisation within the first hour following exposure to a known substance. Figure 4 summarises the most common poisons and their antidotes. 8. FIGURE 4.
[24] The role of toxicology in climate change: Understanding the risks of ... — Capturing the full spectrum of climate-related toxicological risks instead requires a systems-level approach that incorporates environmental science, epidemiology, and toxicology (Fawzy et al., 2020). Adaptive regulatory frameworks, capable of rapid response to emerging threats, are necessary for this purpose, and policymakers must understand this.
[26] Microplastics: Their effects on the environment, human health, and ... — They can enter the human body through inhalation, ingestion, or skin contact, causing various health hazards, including cell injury, hormone disruption, and cardiovascular disease. On the other hand, these microplastics also significantly impact soil and plant growth, reducing yields and other negative consequences for the plants.
[35] Mechanisms of Toxicity | Casarett and Doull's Toxicology: The Basic ... — An understanding of the mechanisms of toxicity is of both practical and theoretical importance. Such information provides a rational basis for interpreting descriptive toxicity data, estimating the probability that a chemical will cause harmful effects, establishing procedures to prevent or antagonize the toxic effects, designing drugs and industrial chemicals that are less hazardous, and
[36] Welcome to ToxTutor - Toxicology MSDT — Dose Response The dose-response relationship is an essential concept in toxicology. It correlates exposures with changes in body functions or health. In general, the higher the dose, the more severe the response. The dose-response relationship is based on observed data from experimental animal, human clinical, or cell studies.
[37] Dose-Response Relationship - an overview - ScienceDirect — The individual dose–response relationship, which describes the response of an individual organism to varying doses of a chemical, is often referred to as a “graded” response because the measured effect is continuous over a range of doses (Fig. 1.18). In this chapter, we introduce the concepts of dose, response, and effect, as well as the relationships between them and the curves that illustrate them. In addition to determining whether the test substance induces an effect (toxic or therapeutic) above any background effect observed in control subjects, it is of interest to determine whether such a compound-related response increases as the dose increases (i.e., whether a dose-response relationship exists). In this chapter, we introduce the concepts of dose, response, effect, and the relationships between them and the curves that illustrate them.
[38] Patient's History - Toxicology — Introduction to Patient History in Toxicology In the field of toxicology, understanding a patient's history is crucial for diagnosing and managing cases of poisoning or exposure to toxic substances. A comprehensive patient history not only aids in identifying the offending agent but also in determining the right course of action.
[39] Taking an Exposure History - Environmental Medicine - NCBI Bookshelf — An exposure history should be taken on every patient. It is of particular importance if the patient's illness occurs at an atypical age or is unresponsive to treatment. The clinician must also keep in mind that many organ systems are affected by toxic exposure . The latency period from exposure to manifestation of disease can vary—ranging
[40] Principles of assessment and diagnosis of the poisoned patient — Assessment of the patient with acute poisoning includes history-taking, assessment of airway, breathing, circulation and consciousness level, physical examination to elicit relevant clinical signs and appropriate investigations. Diagnosis is usually based on history, recognition of toxidromes (when present) and results of investigations.
[41] Assessment Assessment and diagnosis of the poisoned patient — In unconscious patients, a history from friends or relatives is helpful, and the diagnosis can often be inferred from tablet bottles or a 'suicide note' brought by the paramedics, or made by exclusion of other causes. Self-poisoning must always be considered in the differential diagnosis in any patient with an altered level of consciousness.
[44] History of Toxicology - ScienceDirect — This chapter gives a striking account of the history of toxicology. The word "toxicology" comes from the Greek word for poison (toxicon) and scientific study (logos), and was coined in the 17th century. Toxicology was originally an empirical science, and did not evolve into a volumetric science until the emergence of chemistry and analytical science. The disciplines of pharmacy, chemistry
[46] Toxicology in Antiquity: Toxicology in Antiquity Volume I - Goodreads — The book explains that before scientific research methods were developed, toxicology thrived as a very practical discipline. People living in ancient civilizations readily learned to distinguish safe substances from hazardous ones, how to avoid these hazardous substances, and how to use them to inflict harm on enemies.
[47] Book Review: History of Toxicology and Environmental Health-Toxicology ... — Volume I is divided into 12 chapters. Chapter 1—entitled "Toxicology in Ancient Egypt"—sets the stage by explaining that snakes, scorpions, plant, and mineral toxins fit into the Maat or "order of things in the world." This is known through numerous ancient writings but primarily the Brooklyn (525-600 BCE), Berlin (1200 BCE), Ebers (1656 BCE), and Edwin Smith (1650-1550 BCE) Papyri
[48] The history of poisoning: from ancient times until modern ERA — Knowledge of toxic substances is likely as old as the mankind. In the Middle Age, Paracelsus claimed that in the world there is no non-toxic substance that the therapeutic and toxic properties of substances are indistinguishable up to a single parameter-dose. This postulate still belongs among the basic pillars of modern toxicology.
[50] Historical Context of Poison Control — At the beginning of the 20th century, there was no modern specialty of toxicology, no poison control centers, no oversight of pharmaceutical manufacturing or drug labeling, and little knowledge regarding the treatment of poisonings in the United States. Household and occupational toxic hazards were poorly understood. As public health concepts were in their formative stages, surveillance of
[52] Ethical, legal, societal, and professional issues in toxicology — What ethical obligations do, toxicologists have in light of this information and its effects on human health and the environment (Gilbert and Eaton, 2009)? With the increased understanding of the negative health consequences of chemicals and the development of civilization, ethical concerns about toxicology have grown increasingly prominent.
[54] Analytical Methods in Toxicology | Analytical Chemistry - ACS Publications — Recent developments in analytical methods for toxicological research cover a diverse range. This virtual issue represents some of the advances in the development of analytical methods and their applications in chemical toxicology. Mass spectrometry and its hyphenation with chromatography and capillary electrophoresis, field-flow fractionation
[58] PDF — Keywords: Contaminants • Public health • Environmental assessment • Analytical toxicology Analytical Toxicology Methods and Applications in Environ-mental Assessment Maria D. Discussion In recent years, significant advancements have been made in analytical techniques, enhancing the capabilities of toxicologists to address emerging challenges in environmental assessment: HRMS offers superior mass resolution and accuracy compared to conventional mass spectrometry systems, enabling the detection and identification of a broader range of analytes with enhanced sensitivity and selectivity. By combining multi-omics data with advanced analytical techniques, toxicologists can assess the complex interactions between environmental exposures and biological responses, identify early indicators of adverse health effects, and develop predictive models for risk assessment and regulatory decision-making.
[59] Analytical Methods in Toxicology | Analytical Chemistry - ACS Publications — Analytical chemistry plays an important role in chemical toxicology research. Various analytical techniques and assays enable the determination of the dose or concentration of the test chemical. Furthermore, the need to characterize metabolites, detect molecular interactions, and understand the toxic effects drives the development of new
[62] Poisons, plants and Palaeolithic hunters - University of Cambridge — Few hunter-gatherer societies remain today but all the groups that have survived employ poisons. The Yanomami people of the Amazonian rainforest use curare - a mix of Strychnos genus plants - to poison their arrows. In Africa, a variety of different plants are used to make poisons. Acokanthera, Strophantus and Strychnos are the most common.
[64] From Poisonous to Protective: The Surprising Myths of Common Plants — The ancient herbalists understood this dichotomy well, utilizing plants in ways that maximized their benefits while minimizing risks. For instance, certain plants used in traditional medicine have been found effective in treating various ailments, but their improper use can lead to adverse effects. Historically, cultures worldwide have relied
[65] History of Toxicology - ScienceDirect — This chapter gives a striking account of the history of toxicology. The word "toxicology" comes from the Greek word for poison (toxicon) and scientific study (logos), and was coined in the 17th century.Toxicology was originally an empirical science, and did not evolve into a volumetric science until the emergence of chemistry and analytical science.
[66] The History of Toxicology: the Long and Short of it - Academia.edu — The History of Toxicology: the Long and Short of it ... Beginning in the late 17th century, however, the vast number of animal, plant, and mineral materials believed to contain healing qualities was collected and arranged, then published, resulting in erudite Latin editions prepared under the sponsorship of elite medical organizations located
[67] Advancements in Computational Toxicology: Integrating Big Data and AI — Increased efforts in the last few years towards computational toxicology, big data, and artificial intelligence have transformed the contemporary mechanism to evaluate toxic effects on human beings and the environmental implications of chemical substances. ... Due to the advances in big data, computational toxicology has been progressing to
[68] Advancing Computational Toxicology in the Big Data Era by Artificial ... — Central to this mission is the advancement of computational toxicology and artificial intelligence approaches to implementing innovative testing methods. In the current big data era, the terms volume (amount of data), velocity (growth of data), and variety (the diversity of sources) have been used to characterize the currently available
[72] The History Of Plant Poisons And How They Have Been Used For Warfare ... — Ancient civilizations such as the Egyptians, Persians, and Chinese discovered and utilized various poisonous plants for both warfare and as assassination tools. For example, the Egyptians used a toxic plant known as Aconite to coat their arrowheads, ensuring that their enemies would suffer a slow and painful death upon being struck.
[82] Recent Advances in Drug Discovery Toxicology - Bowen Tang, Vijay More, 2023 — This review describes some recent research methods in drug discovery toxicology, including in vitro cell and organ-on-a-chip, imaging systems, model organisms (C. elegans, Danio rerio, and Drosophila melanogaster), and toxicogenomics in modern toxicology testing.
[84] ToxAIcology - The evolving role of artificial intelligence in advancing ... — Toxicology has undergone a transformation from an observational science to a data-rich discipline ripe for artificial intelligence (AI) integration. ... 2023;40(4):559-570. doi: 10.14573/altex.2309191. ... (QSARs), recent advances with deep neural networks, and emerging trends. The promises and challenges of AI adoption for predictive
[85] The evolving role of investigative toxicology in the ... - Nature — Advertisement View all journals Search Log in Explore content About the journal Publish with us Subscribe Sign up for alerts RSS feed nature nature reviews drug discovery perspectives article Perspective Published: 13 February 2023 The evolving role of investigative toxicology in the pharmaceutical industry Francois Pognan ORCID: orcid.org/0000-0001-7033-20331, Mario Beilmann2, Harrie C. M. Boonen3, Andreas Czich4, Gordon Dear5, Philip Hewitt6, Tomas Mow7, Teija Oinonen8, Adrian Roth9, Thomas Steger-Hartmann10, Jean-Pierre Valentin ORCID: orcid.org/0000-0002-3599-915511, Freddy Van Goethem12, Richard J. Weaver ORCID: orcid.org/0000-0001-6439-603013 & … Peter Newham ORCID: orcid.org/0000-0002-0955-408014 Show authorsNature Reviews Drug Discovery volume 22, pages 317–335 (2023)Cite this article 59k Accesses 38 Altmetric Metrics details Subjects Drug safety Preclinical research Toxicology Abstract For decades, preclinical toxicology was essentially a descriptive discipline in which treatment-related effects were carefully reported and used as a basis to calculate safety margins for drug candidates. In recent years, however, technological advances have increasingly enabled researchers to gain insights into toxicity mechanisms, supporting greater understanding of species relevance and translatability to humans, prediction of safety events, mitigation of side effects and development of safety biomarkers. Consequently, investigative (or mechanistic) toxicology has been gaining momentum and is now a key capability in the pharmaceutical industry. Here, we provide an overview of the current status of the field using case studies and discuss the potential impact of ongoing technological developments, based on a survey of investigative toxicologists from 14 European-based medium-sized to large pharmaceutical companies.
[88] Artificial Intelligence in Drug Toxicity Prediction: Recent Advances ... — Toxicity prediction is a critical step in the drug discovery process that helps identify and prioritize compounds with the greatest potential for safe and effective use in humans, while also reducing the risk of costly late-stage failures. It is estimated that over 30% of drug candidates are discarded owing to toxicity. Recently, artificial intelligence (AI) has been used to improve drug
[89] Advancing Computational Toxicology by Interpretable Machine Learning — Chemical toxicity evaluations for drugs, consumer products, and environmental chemicals have a critical impact on human health. Traditional animal models to evaluate chemical toxicity are expensive, time-consuming, and often fail to detect toxicants in humans. Computational toxicology is a promising alternative approach that utilizes machine learning (ML) and deep learning (DL) techniques to
[90] Regulatory toxicology in the twenty-first century: challenges ... — The advent of new testing systems and "omics"-technologies has left regulatory toxicology facing one of the biggest challenges for decades. That is the question whether and how these methods can be used for regulatory purposes. The new methods undoubtedly enable regulators to address important open questions of toxicology such as species-specific toxicity, mixture toxicity, low-dose
[91] New approach methodologies in human regulatory toxicology - Not if, but ... — New approach methodologies in human regulatory toxicology - Not if, but how and when! ... 13 NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), National Institute of Environmental Health ... and hesitance from relevant stakeholders, are major challenges for the implementation of NAMs in a broader context.
[94] Ethical principles and scientific advancements: In vitro, in silico ... — Collaborative efforts between researchers, industries, and regulatory bodies are anticipated to lead to standardized protocols and validation frameworks. Streamlining the regulatory approval process for in vitro and in silico methods, along with invertebrate models, will facilitate their integration into standard toxicological assessments.
[139] What is Toxicology? - Toxicology Education Foundation — Establishing safe levels after production and use of a chemical so that the public continues to be protected from harmful levels is one of the main roles filled by regulatory toxicologists and others working outside of a government setting on similar issues related to risk assessment. These next two videos were produced by toxicology students challenged with addressing the question: Why would you want to become a toxicologist? A toxicology encyclopedia offering articles and other resources addressing a variety of chemical toxicity issues that will further inform viewers of some of current issues toxicologists are addressing. Risk, History of Toxicology, Occupational Safety and Health, Radiation, Venomous or Poisonous – Animals, Plants, Mushrooms and More, Reproductive and Developmental Toxicity Hazards,
[143] Clinical and Forensic Signs Resulting from Exposure to Heavy Metals and ... — Acute toxicity which results from exposure to large doses, within a short time exposure, as well as its presentation are usually dramatic. The most common presentations vary with the form of exposure: respiratory symptoms in cases of inhalation, skin lesions in topical contamination, and, in cases of ingestion, typically mimic acute
[144] Poisoning, Types of Poison: Symptoms & Treatment — Signs and symptoms also vary by: The amount and type of poison Your age and overall health How long you're exposed to the poison. Acute exposures last seconds or minutes, while chronic exposures happen over a long period of time. Symptoms of acute poison exposure There are many possible symptoms of acute poisoning.
[154] Assessment of Toxicity - Science and Judgment in Risk Assessment - NCBI ... — This chapter discusses the methods used to evaluate the toxicity of a substance for the purpose of health risk assessment. Evaluation of toxicity involves two steps: hazard identification and dose-response evaluation. Hazard identification includes a description of the specific forms of toxicity (neurotoxicity, carcinogenicity, etc.) that can be caused by a chemical and an evaluation of the
[156] Welcome to ToxTutor - Toxicology MSDT — Dose Response The dose-response relationship is an essential concept in toxicology. The dose-response relationship is based on observed data from experimental animal, human clinical, or cell studies. Knowledge of the dose-response relationship establishes: The dose-response curve is a visual representation of the response rates of a population to a range of doses of a substance, as demonstrated in Animation 2. The graph of a dose-response relationship typically has an "s" shape. 1) The quantity of a substance administered to an individual over a period of time or in several individual doses is known as the: 4) The dose at which a toxic effect is first encountered is called the: 5) The dose-response relationship helps a toxicologist determine: b) the threshold dose
[157] Basics of Dose-Response - Toxicology Education Foundation — Basics of Dose-Response - Toxicology Education Foundation While in this example we’re looking at the benefit from a pain reliever, the toxicologist uses this same kind of dose-response curve to determine what dose it takes to cause harmful effects. For the toxicologist, this type of dose-response curve helps determine what percentage of people may suffer harm at any specific dose. Example of Dose-Response-Alcohol. Summary: Because hazard, exposure, dose and response are terms commonly used by toxicologists to describe the safe use of chemicals it is important for everyone concerned about chemical exposures to understand what they mean and how you can use them to understand safe exposure.
[159] 3.2: Factors Affecting Toxicity - Chemistry LibreTexts — Factors Influencing Toxicity. In some instances, individuals can have unpredictable reactions, or idiosyncratic responses, to a drug or other substance.An idiosyncratic response is uncommon, and it is sometimes impossible to understand whether it is the result of a genetic predisposition or has some other cause such as the status of the immune system.
[160] PDF — Biological factors affecting toxic response Diseases •Acute and chronic liver injury such as hepatitis, cirrhosis, toxic hepatitis, porphyria, and liver tumors will affect the biotransformation. •Renal disease can cause disturbances in excretion of a chemical thus increasing its toxicity.
[178] 10 Reasons Why Toxicology Is Important - The Important Site — Toxicology Is Fundamental to Increasing Public Safety Toxicology studies provide critical resources for increasing public safety and reducing public health hazards. By identifying and analyzing toxic chemicals, toxicologists determine what exposure to toxins can potentially cause and minimize the adverse health effects accordingly.
[179] Public Health Toxicology - Environmental Health — The Public Health Toxicology Program is responsible for two distinct areas of public health concern: the identification of potential health hazards resulting from exposure to certain chemical or biological agents, and the assessment and subsequent recommendations to abate or reduce any resulting health effects.
[191] 40.5.4: National Regulatory Toxicology - Chemistry LibreTexts — Example agencies that set national toxicology regulations in the U.S.: Environmental Protection Agency (EPA) Food and Drug Administration (FDA) Occupational Safety and Health Administration (OSHA) Consumer Product Safety Commission (CPSC) All agencies aim to set regulations to protect against adverse health effects from exposure to substances.
[192] 5.1: Introduction to Regulatory Toxicology - Chemistry LibreTexts — Often regulations are developed by experts in a governmental authority to enforce legislation. An example of a regulation is the Food Quality Protection Act (FQPA) passed by the U.S. Congress and signed into law by the President in 1996. Policies and guidelines are principles and approaches that clarify and interpret regulations.
[193] The impact of toxicology on public health policy and service ... - PubMed — The Division of Toxicology, Agency for Toxic Substances and Disease Registry (ATSDR) has a Congressional mandate to develop toxicological profiles for chemicals of greatest concern at hazardous waste sites. These chemical profiles provide a comprehensive evaluation and interpretation of the health e …
[194] The Precautionary Principle Also Applies to Public Health Actions — PUBLIC HEALTH ADVOCATES around the world have increasingly invoked the precautionary principle as a basis for preventive actions.1 - 9 This has been particularly true for environmental and food safety issues, in which the precautionary principle has moved from being a rallying cry for environmental advocates to a legal principle embodied in international treaties.2, 6, 8 - 11 Definitional
[195] Green Veterinary Pharmacology and Toxicology: A "One ... - Frontiers — Green Veterinary Pharmacology and Toxicology represents a branch of veterinary pharmacology which should be implemented as a complementary and sustainable method to reduce the use of chemicals and minimize the phenomena of drug resistance and the persistence of residues in the environment, from a "One Health" approach perspective.
[197] Perspectives in Veterinary Pharmacology and Toxicology - PMC — By the mid-1950s, pharmacology and toxicology were a highly active area of veterinary medicine; veterinary pharmacology and toxicology emerged as new disciplines, closely related, because they were involved in developing new compound, particularly new antimicrobials and antiparasitics to control infection diseases, and analgesic/non-steroidal anti-inflammatory drugs affecting different animal species. Like veterinary medicine, veterinary pharmacology and toxicology is not an easy matter because of multiplicity of animal species as well as breed, age, sex, and (patho)physiological status concerned that may respond differently to certain drugs, food, feed, pesticides, and industrial products as well as contaminants or toxins.
[198] Recent Advances in Veterinary Pharmacology and Toxicology - MDPI — Nowadays, veterinary pharmacology and toxicology should be regarded as disciplines contributing to the "One Health" paradigm, reducing risk at the animal-human ecosystem. The use of antibiotics plays a crucial role in maintaining the safety, health, and rapid development of the animal husbandry industry. In the past 30 years, the fields
[199] Examples of Environmental Impact from Toxic Pollution — Environmental pollution poses threats to ecosystems and human health, with toxic pollutants being a primary concern. These substances infiltrate air, water, and soil, leading to detrimental effects on biodiversity and potentially causing long-term damage to natural resources.
[200] Chemical Pollution: How Our Daily Lives are Affected by Toxic Chemicals — Environmental Consequences Pollutants with toxic properties have severe effects on the environment and society. One is the contamination of ecosystems; the pollutants alter the normal functioning of ecosystems. Wildlife is also affected by toxic substances, and effects include ill health, reproductive impairments, and fatalities.
[202] Pesticides have negative effects on non-target organisms — Pesticides affect a diverse range of non-target species and may be linked to global biodiversity loss. The magnitude of this hazard remains only partially understood. We present a synthesis of
[207] Chemical Risk Assessment: Traditional vs Public Health Perspectives — A public health perspective would focus on the adverse health outcome of concern with multiple data streams, informing our understanding of hazard and exposure in the context of public health decisions related to that outcome and not necessarily focused on just 1 chemical or class of chemicals.
[208] Chemical exposures, health and environmental justice in communities ... — Chemical exposures, health and environmental justice in communities living on the fenceline of industry - PMC More people are living near oil and gas development due to the expansion of unconventional extraction techniques as well as near industrial animal operations, both with suggestive evidence of increased exposure to hazardous pollutants and adverse health effects. While assessing health impacts due to chemical exposures in communities adjacent to industrial activities is challenging due to the common lack of baseline environmental monitoring and small sample size issues for epidemiologic studies, recent advancements in the literature have used innovative strategies including community-engaged research, biomonitoring, and natural experiments to help elucidate these links.
[210] A science-based agenda for health-protective chemical assessments and ... — The manufacture and production of industrial chemicals continues to increase, with hundreds of thousands of chemicals and chemical mixtures used worldwide, leading to widespread population exposures and resultant health impacts. Low-wealth communities and communities of color often bear disproportionate burdens of exposure and impact; all compounded by regulatory delays to the detriment
[211] Challenges Faced by Toxicologists in the Modern Era — Toxicologists face significant challenges due to limited funding for research and testing. Toxicologists face significant challenges due to the increased use of chemicals in products and industries. Another challenge toxicologists face is identifying and assessing the effects of chemical mixtures. Addressing these challenges requires collaboration between toxicologists, regulatory agencies, and the public to ensure safety and protect health. Balancing scientific evidence with public health protection remains a significant challenge for toxicologists. Additionally, toxicologists face challenges in communicating their findings to the public. In summary, toxicologists face numerous challenges in the modern era, including misinformation, public mistrust, and the need for effective communication. Toxicologists face several challenges in the modern era that impact their ability to ensure public health and safety.
[212] Hot topics in toxicology - PubMed — Toxicology is facing new challenges in addressing issues that will have an impact on developing and meeting new regulatory guidance, public health protection and research directions. ... assess the associated risks, and reduce the uncertainties. This discussion presents an overview of the associated regulatory mandates, how various programs are
[221] Hazard assessment of nanomaterials: how to meet the requirements for ... — Background Hazard and risk assessment of nanomaterials (NMs) face challenges due to, among others, the numerous existing nanoforms, discordant data and conflicting results found in the literature, and specific challenges in the application of strategies such as grouping and read-across, emphasizing the need for New Approach Methodologies (NAMs) to support Next Generation Risk Assessment (NGRA
[225] Risk Communication strategies - Toxicology — Conclusion Effective risk communication in toxicology is vital for ensuring public safety and health. By understanding the audience, using appropriate tools and channels, and maintaining transparency and credibility, toxicologists can effectively convey risks and promote informed decision-making. As with any communication process, continuous evaluation and adaptation of strategies are
[226] Communication at the Core of Effective Public Health — Public health recognizes that health is profoundly affected by the social, political, environmental, and behavioral factors with which people live.5,7 Public health communication embraces this ecological perspective by encouraging multilevel communication strategies and interventions, such as tailored messages at the individual level, targeted messages at the group level, social marketing at
[233] Funding Details - Toxicology — Funding allocation in toxicology is typically influenced by the priorities of the funding body. For instance, governmental agencies may prioritize research that addresses public health concerns, such as the impact of pollutants or the safety of consumer products.
[235] Navigating the bridge between wet and dry lab toxicology research to ... — As a result, the field of toxicology is currently plagued with the following data analysis problems (Sobus et al, 2018): we need to better analyze large datasets, including high-dimensional data (Figure 1) and (Rager et al, 2013) we need to better advise and train “wet lab” scientists to analyze such dataset. The aim of this perspective is to i) draw attention to the current need to improve data analyses for large datasets, ii) highlight some example methods of organizing and analyzing high-dimensional data, and iii) describe challenges that now need to be addressed to improve data analyses in toxicology research, all of which represent issues of current discussion between wet lab and dry lab scientists. These studies, including review studies, demonstrate the utility of supervised ML methods when incorporating high-dimensional data into toxicological research (Ekins, 2014; Omer et al, 2014; Idakwo et al, 2018).
[246] Regulatory Challenges - Toxicology — Globalization has led to increased trade and movement of goods, necessitating harmonization of regulatory standards. However, differences in regulatory requirements across countries can complicate compliance for multinational companies. Efforts like the ICH work towards aligning standards but achieving full harmonization remains challenging.
[247] Regulatory toxicology in the twenty-first century: challenges ... — The advent of new testing systems and "omics"-technologies has left regulatory toxicology facing one of the biggest challenges for decades. That is the question whether and how these methods can be used for regulatory purposes. The new methods undoubtedly enable regulators to address important open questions of toxicology such as species-specific toxicity, mixture toxicity, low-dose
[250] Challenges Faced by Toxicologists in the Modern Era — Toxicologists face significant challenges due to limited funding for research and testing. Toxicologists face significant challenges due to the increased use of chemicals in products and industries. Another challenge toxicologists face is identifying and assessing the effects of chemical mixtures. Addressing these challenges requires collaboration between toxicologists, regulatory agencies, and the public to ensure safety and protect health. Balancing scientific evidence with public health protection remains a significant challenge for toxicologists. Additionally, toxicologists face challenges in communicating their findings to the public. In summary, toxicologists face numerous challenges in the modern era, including misinformation, public mistrust, and the need for effective communication. Toxicologists face several challenges in the modern era that impact their ability to ensure public health and safety.
[252] Regulatory Issues: Challenges and Implications — Key factors contributing to regulatory challenges include: Dynamic legislation: Regulations often evolve to keep pace with societal and technological changes, requiring constant adaptation. Globalization: International trade and cooperation necessitate compliance with multiple jurisdictions, often leading to conflicting regulatory requirements.