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Related Concept Videos

Toxicity Testing in Animals01:23

Toxicity Testing in Animals

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Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...
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Toxicokinetics: Overview01:21

Toxicokinetics: Overview

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Studies that assess how a drug is absorbed, distributed, metabolized, and excreted (ADME) at toxic doses are termed toxicokinetics. Understanding toxicokinetics helps predict adverse drug reactions (ADRs) and manage toxicity in humans.Toxicokinetics differs from pharmacokinetics mainly in the dose levels studied, with toxicokinetics focusing on higher toxic doses. The kinetics at these levels can be non-linear due to altered physiological processes. Toxicodynamics examines the relationship...
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Drug Toxicity: Dose-Dependent Reactions01:24

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Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
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Drug Toxicity: Overview01:00

Drug Toxicity: Overview

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Drug toxicity quantifies the harm a compound causes to an organism, varying by dose and potentially impacting whole systems or specific organs like the liver. Toxic reactions may arise from venomous insect or spider bites, with effects ranging from mild symptoms to severe outcomes such as brain damage or death. Common forms of acute poisoning include ethanol intoxication and overdose of pain or fever medications, with substances like GHB and heroin being particularly lethal at doses close to...
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Toxic Reactions: Overview01:26

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When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
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Drug Toxicity: Risk factors01:24

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Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
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Assessment of Chemical Toxicity in Adult Drosophila Melanogaster
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Evidence-Based Toxicology.

Sebastian Hoffmann1, Thomas Hartung2,3, Martin Stephens2

  • 1seh consulting + services, Paderborn, Germany. sebastian.hoffmann@seh-cs.com.

Advances in Experimental Medicine and Biology
|September 28, 2016
PubMed
Summary
This summary is machine-generated.

Evidence-based toxicology (EBT) enhances toxicological risk assessment by adopting principles from evidence-based medicine. This approach improves the validation of toxicological test methods for modern challenges.

Keywords:
Diagnostic test assessmentEvidence-based toxicologyMechanistic validationTest method assessmentValidation

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Area of Science:

  • Toxicology
  • Risk Assessment
  • Evidence-Based Medicine

Background:

  • Evidence-based toxicology (EBT) emerged in 2005, inspired by evidence-based medicine (EBM).
  • EBT focuses on toxicological risk assessment, causation, and the evaluation of test methods.
  • Systematic reviews and evidence quality assessment are key components gaining traction in toxicology.

Purpose of the Study:

  • To explore the role of Diagnostic Test Assessment (DTA) in addressing challenges in toxicological test validation.
  • To highlight how EBT principles can be applied to pathway-based toxicology for mechanistic validation.
  • To propose EBT as a framework for modernizing toxicological test assessment and validation.

Main Methods:

  • Drawing parallels between diagnostic test assessment in medicine and toxicological test evaluation.
  • Identifying Diagnostic Test Assessment (DTA) as a resource for improving toxicological test validation.
  • Applying EBT principles to retrospective mechanistic validation in pathway-based toxicology.

Main Results:

  • Diagnostic Test Assessment (DTA) offers solutions for validating toxicological tests, especially when reference standards are imperfect.
  • EBT approaches provide objectivity, transparency, and consistency for mechanistic validation in toxicology.
  • The integration of EBT is crucial for adapting toxicological assessment to 21st-century demands.

Conclusions:

  • Evidence-based toxicology provides a robust framework for evaluating toxicological data and methods.
  • Adopting EBT principles is essential for advancing the field of toxicology and ensuring reliable risk assessment.
  • The systematic evaluation of evidence is key to meeting the evolving challenges in toxicology.