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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...
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,...
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...
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...
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
Drug Toxicity: Risk factors01:24

Drug Toxicity: Risk factors

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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  1. Home
  3. Multi-omics Integration Into Adverse Outcome Pathway Framework: Principles, Progress, And Prospects For Next-generation Toxicological Risk Assessment.
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  3. Multi-omics Integration Into Adverse Outcome Pathway Framework: Principles, Progress, And Prospects For Next-generation Toxicological Risk Assessment.

Related Experiment Video

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

Multi-Omics Integration Into Adverse Outcome Pathway Framework: Principles, Progress, and Prospects for

Rajesh Pamanji1, Ragothaman Prathiviraj2, Gisha Sivan3

  • 1Department of Microbiology, Pondicherry University, Puducherry, India.

Environmental and Molecular Mutagenesis
|June 3, 2026

View abstract on PubMed

Summary
This summary is machine-generated.
Keywords:
adverse outcome pathwayepigenomicsmetabolomicsmulti‐omicsproteomicstranscriptomics

Related Experiment Videos

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

Multi-omics technologies enhance adverse outcome pathway (AOP) construction by integrating diverse data layers. This approach improves mechanistic understanding and quantitative utility for next-generation chemical risk assessment.

Area of Science:

  • Mechanistic toxicology
  • Computational biology
  • Biomarker discovery

Background:

  • Adverse outcome pathway (AOP) framework aids mechanistic toxicology but traditionally uses limited, single-layer data.
  • This limitation restricts mechanistic resolution and quantitative application in regulatory risk assessment.
  • Multi-omics technologies offer rich, multi-scale molecular data to enhance AOPs.

Purpose of the Study:

  • To systematically review how different omics layers (transcriptomics, proteomics, metabolomics, epigenomics) contribute to AOP development.
  • To discuss emerging frameworks for integrating these omics data into AOP networks.
  • To assess quantitative AOP (qAOP) strategies and identify knowledge gaps for regulatory acceptance.

Main Methods:

  • Systematic review of multi-omics technologies (transcriptomics, proteomics, metabolomics, epigenomics, single-cell) in AOP development.
  • Examination of transcriptome-guided key event (KE) identification and proteomic confirmation of KE-to-KE relationships (KERs).
  • Assessment of metabolomics for phenotypic linkage, epigenomics for persistent effects, and single-cell approaches for resolution.

    • Main Results:

    • Each omics layer offers unique contributions: transcriptomics for KE identification, proteomics for KERs, metabolomics for phenotypic linkage, and epigenomics for long-term effects.
    • Transcriptomic points of departure (tPODs) from short-term exposures show concordance with chronic apical endpoints.
    • Single-cell omics can overcome limitations of bulk assays by providing cellular resolution.

    Conclusions:

    • Integrating multi-omics data significantly enhances AOPs' mechanistic resolution and quantitative utility for chemical risk assessment.
    • Key knowledge gaps include incomplete KE annotation, lack of standardized bioinformatics pipelines, and regulatory hurdles for omics-derived values.
    • Further research and standardized frameworks are needed to accelerate the regulatory acceptance of multi-omics-informed AOPs.