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Related Concept Videos

Preclinical Development: Overview01:28

Preclinical Development: Overview

Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
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...
Pharmacovigilance01:19

Pharmacovigilance

Post-marketing surveillance is a critical component of pharmaceutical regulation, often uncovering unanticipated adverse drug reactions (ADRs) once a drug is widely used over an extended period.
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
Clinical Trials: Overview01:11

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches01:23

Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches

Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
Clinical Trials01:16

Clinical Trials

Clinical trials are prospective experimental studies conducted on humans to determine the safety and efficacy of treatments, drugs, diet methods, and medical devices. Using statistics in clinical trials enables researchers to derive reasonable and accurate conclusions from the collected data, allowing them to make wise decisions in uncertain situations. In medical research, statistical methods are crucial for preventing errors and bias.
There are four phases in a clinical trial. A phase one...

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Updated: May 26, 2026

Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
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Ultrastructural analysis in preclinical safety evaluation.

Jane A Fagerland1, Henry G Wall, Karamjeet Pandher

  • 1Abbott Laboratories, Abbott Park, Illinois, USA. jane.fagerland@abbott.com

Toxicologic Pathology
|January 5, 2012
PubMed
Summary

Transmission electron microscopy (TEM) was crucial for early biology but declined with new tech. This review highlights TEM's essential role in preclinical toxicity studies for direct ultrastructural data.

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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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11:38

High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)

Published on: May 10, 2016

Area of Science:

  • Cell Biology
  • Toxicologic Pathology
  • Microscopy

Background:

  • Transmission electron microscopy (TEM) revolutionized biological research from the 1940s onwards, enabling detailed ultrastructural studies.
  • The advent of molecular techniques and confocal fluorescence microscopy led to a decline in TEM usage due to faster data acquisition and simpler training.
  • TEM's application in toxicologic pathology mirrored its trend in broader biological research.

Purpose of the Study:

  • To review the historical significance and current relevance of TEM in biological and toxicologic research.
  • To emphasize TEM's irreplaceable value in preclinical safety evaluation and mechanistic studies.
  • To advocate for the continued use and best practices in ultrastructural evaluation.

Main Methods:

  • Historical review of TEM's role in biological sciences.
  • Analysis of TEM's application in toxicologic pathology.
  • Discussion of TEM's contribution to preclinical safety testing.

Main Results:

  • TEM was foundational to early cellular and molecular biology but faced reduced usage with newer technologies.
  • Despite declining popularity, TEM remains indispensable for providing direct, unequivocal data in preclinical toxicity studies.
  • Ultrastructural visualization via TEM can link subcellular changes to other toxicological endpoints.

Conclusions:

  • TEM continues to be an essential tool in preclinical safety evaluation and mechanistic investigations.
  • The direct visualization of subcellular structures by TEM offers unique insights not achievable with other methods.
  • Adoption of best practices in ultrastructural evaluation is encouraged to maximize TEM's utility in modern research.