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Related Concept Videos

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,...
Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis00:59

Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis

Noncompartmental analyses offer an alternative method for describing drug pharmacokinetics without relying on a specific compartmental model. In this approach, the drug's pharmacokinetics are assumed to be linear, with the terminal phase log-linear. This assumption allows for simplified analysis and interpretation of the drug's behavior in the body.
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This relationship...
Nonlinear Pharmacokinetics: Overview01:19

Nonlinear Pharmacokinetics: Overview

Nonlinear or dose-dependent pharmacokinetics is a phenomenon that occurs when the pharmacokinetic parameters of certain drugs deviate from linear pharmacokinetics at higher doses. These drugs do not follow the expected first-order kinetics, where the rate of drug elimination is directly proportional to the drug concentration. Instead, they exhibit a nonlinear relationship, which can be attributed to several factors.
Nonlinearity can arise due to the saturation of plasma protein-binding or...
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...
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...

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Functional Evaluation of Biological Neurotoxins in Networked Cultures of Stem Cell-derived Central Nervous System Neurons
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National Toxicology Program Position Statement on Informed ("Nonblinded") Analysis in Toxicologic Pathology

Robert C Sills1, Mark F Cesta1, Cynthia J Willson2

  • 1Division of the National Toxicology Program, Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.

Toxicologic Pathology
|September 17, 2019
PubMed
Summary
This summary is machine-generated.

The National Toxicology Program (NTP) uses rigorous histopathological evaluation in toxicity studies. An informed approach, rather than masked analysis, is supported to ensure accurate diagnoses by comparing treated and control groups.

Keywords:
National Toxicology Programblinded evaluationblindednesshistopathologyinformed analysismasked analysis

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Area of Science:

  • Toxicology
  • Pathology
  • Animal Studies

Background:

  • Histopathological evaluation is crucial for the National Toxicology Program's (NTP) toxicity and carcinogenicity studies.
  • NTP employs a multi-step peer review process with experienced toxicological pathologists and standardized terminology.
  • Ancillary data, including organ weights and clinical pathology, support diagnostic corroboration.

Purpose of the Study:

  • To describe the NTP's peer review process for histopathological evaluations.
  • To discuss the role and limitations of masked analysis in these studies.
  • To advocate for an informed approach to histopathological evaluation.

Main Methods:

  • Rigorous peer review by multiple toxicological pathologists.
  • Use of standardized terminology in evaluations.
  • Corroboration of diagnoses with ancillary data (e.g., organ weights, clinical pathology).
  • Limited use of masked analysis for subtle lesions or severity scoring during Pathology Working Groups.

Main Results:

  • The NTP's peer review process involves multiple experts and standardized methods.
  • Ancillary data are integrated to strengthen diagnostic confidence.
  • Masked analysis, while used selectively, can hinder direct comparison with concurrent controls.

Conclusions:

  • The NTP's histopathological evaluation process is comprehensive and relies on expert review and supporting data.
  • An informed approach, allowing comparison between treated and control groups, is essential for accurate histopathological assessment in toxicity studies.
  • The NTP prioritizes an informed evaluation strategy over fully blinded assessments to maintain diagnostic integrity.