Related Experiment Video
Updated: May 17, 2026
17:28
Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Systems toxicology from genes to organs
John Jack1, John Wambaugh, Imran Shah
1U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.
Methods in Molecular Biology (Clifton, N.J.)
|October 23, 2012
Summary
This review explores systems toxicology, integrating systems biology and computational approaches to link molecular responses to human health effects. It highlights current advancements and future directions in understanding toxicological impacts.
Area of Science:
- Integrative toxicology and computational biology.
Background:
- Historical overview of systems thinking in biology.
- Evolution of toxicology from physiologically based models to molecular systems biology.
- Leveraging advances in computational modeling, informatics, and biotechnology.
Purpose of the Study:
- To provide a comprehensive overview of systems toxicology methods and techniques.
- To bridge laboratory measurements of molecular responses to adverse human health outcomes.
- To identify key scientific gaps and propose innovative solutions.
Main Methods:
- Review of historical and current literature in systems biology and toxicology.
- Discussion of computational modeling, informatics, and biotechnology applications.
- Analysis of the translation from molecular responses to organ-level effects.
Main Results:
- Demonstration of how systems biology and toxicology are converging.
- Identification of pathways to translate xenobiotic perturbation data to human health risks.
- Highlighting the interdisciplinary nature of modern toxicology.
Conclusions:
- Systems toxicology offers a powerful framework for understanding complex biological responses to chemical exposures.
- Future directions involve integrating diverse data streams to predict adverse outcomes.
- This field holds significant promise for improving human health risk assessment.
Related Concept Videos
01:26Toxic 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 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,...
01:36Types of Toxins
Humans continually engage with an environment rich in potentially harmful chemicals. These are introduced to our bodies through inhalation, ingestion, or skin contact. These chemicals exist in various forms, such as air and environmental pollutants, agricultural chemicals, organic solvents, and heavy metals.
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
01:21Toxicokinetics: 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...
01:23Toxicity 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...
01:24Drug 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...
01:25Bioactivation 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...