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Related Concept Videos

Toxicokinetics: Overview01:21

Toxicokinetics: Overview

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...
Toxicity Testing in Animals01:23

Toxicity Testing in Animals

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...
Toxic Reactions: Overview01:26

Toxic Reactions: Overview

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.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

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...
Drug Toxicity: Overview01:00

Drug Toxicity: Overview

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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Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
17:28

Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation

Published on: June 17, 2015

[Development of new cytoxicity testing systems that include toxicokinetic processes].

Kikuo Komori1, Jun Nada, Shotaro Miyajima

  • 1Institute of Industrial Science, University of Tokyo, Komaba, Meguro-ku, Tokyo, Japan.

Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan
|January 8, 2008
PubMed
Summary

New toxicity testing systems improve upon conventional methods by incorporating toxicokinetic processes. These advanced in vitro models evaluate hazardous chemicals and environmental samples more effectively.

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Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
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Autonomously Bioluminescent Mammalian Cells for Continuous and Real-time Monitoring of Cytotoxicity
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Autonomously Bioluminescent Mammalian Cells for Continuous and Real-time Monitoring of Cytotoxicity

Published on: October 28, 2013

Area of Science:

  • Toxicology
  • In vitro testing
  • Biotechnology

Context:

  • Conventional cytotoxicity tests lack toxicokinetic simulation, limiting whole-body toxicity prediction.
  • Developing advanced in vitro systems to better model human exposure and metabolism.
  • Evaluating hazardous chemicals and environmental samples requires more comprehensive testing methods.

Purpose:

  • To review novel in vitro toxicity test systems that incorporate toxicokinetic processes.
  • To describe a gas exposure system using lung epithelial cells at the air-liquid interface.
  • To introduce a coculture system simulating small intestine permeation and biotransformation, and discuss test miniaturization.

Summary:

  • Presents two novel in vitro toxicity testing systems: a gas exposure system for lung epithelial cells and a double-layered coculture system for intestinal processes.
  • These systems integrate toxicokinetic elements like permeation and biotransformation, overcoming limitations of conventional tests.
  • The review also details efforts in miniaturizing these tests to determine the minimum cell number for physiologically relevant responses.

Impact:

  • Provides more accurate in vitro toxicity assessments by including toxicokinetic factors.
  • Enables better evaluation of hazardous chemicals and environmental samples.
  • Advances the development of miniaturized, physiologically relevant toxicity testing platforms.