Related Experiment Video
Updated: Jan 22, 2026
05:47
In Silico Modeling Method for Computational Aquatic Toxicology of Endocrine Disruptors: A Software-Based Approach Using QSAR Toolbox
Published on: August 28, 2019
14.6K
An Approach for Using In Vitro and In Silico Data to Identify Pharmaceuticals with Potential (Anti-)Estrogenic
Caroline Lucia Pinto1,2, Raanan A Bloom2, James P Laurenson2
1Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA.
Environmental Toxicology and Chemistry
|July 11, 2019
Summary
This study developed a method to screen pharmaceuticals for their potential to disrupt the endocrine system in aquatic vertebrates. It identified numerous drugs that may interact with estrogen receptors (ERs) at environmentally relevant concentrations.
Area of Science:
- Environmental Toxicology
- Endocrinology
- Pharmacology
Background:
- Endocrine-active pharmaceuticals pose risks to aquatic vertebrates due to conserved hormone receptor structures.
- Assessing environmental impacts of pharmaceuticals is crucial for regulatory review.
- Estrogen receptors (ERs) are key targets for endocrine disruption.
Purpose of the Study:
- To develop and demonstrate a screening approach for pharmaceuticals based on ER interaction.
- To prioritize drugs with potential endocrine-disrupting activity in aquatic organisms.
- To evaluate ER agonist and antagonist potential at environmentally relevant concentrations.
Main Methods:
- Utilized Tox21 in vitro assay data for 1123 pharmaceuticals.
- Employed in silico predictions from CERAPP models for an additional 170 pharmaceuticals.
- Calculated Estrogenic Effect Ratio (EER) and Anti-Estrogenic Effect Ratio (AEER) using AC50 and estimated fish tissue concentrations.
Main Results:
- Identified 73 pharmaceuticals as ER agonists and 127 as ER antagonists.
- Confirmed known ER agonists (e.g., estradiol) and antagonists (e.g., raloxifene) with EERs/AEERs > 1.
- Detected four pharmaceuticals with EERs and six with AEERs between 0.1 and 1.
Conclusions:
- The developed approach effectively screens pharmaceuticals for ER interaction potential.
- This method aids in prioritizing drugs needing environmental assessment.
- It supports regulatory decisions for pharmaceuticals that may disrupt vertebrate endocrine systems.
Related Concept Videos
01:26Pharmaceutical Equivalents
189
As defined by regulatory standards, pharmaceutical equivalents require generic drug products to have identical dosage forms and chemically identical active pharmaceutical ingredients (APIs). They must adhere to compendial or applicable standards for potency, content uniformity, disintegration times, and dissolution rates. In the case of modified-release dosage forms, variations in drug content are permissible as long as the delivered amount remains consistent with the innovator drug product.
189
01:10Thermodynamics: Chemical Potential and Activity
1.7K
The effective concentration of a species in a solution can be expressed precisely in terms of its activity. Activity considers the effect of electrolytes present in the vicinity of the species of interest and depends on the ionic strength of the solution. The activity of a species is expressed as the product of molar concentration and the activity coefficient of the species.
The thermodynamic equilibrium constant is more accurately defined in terms of activity rather than concentration.
The thermodynamic equilibrium constant is more accurately defined in terms of activity rather than concentration.
1.7K
02:41Concentration Cells
25.6K
A concentration cell is a type of a voltaic cell constructed by connecting two almost identical half-cells, both based on the same half-reaction and using the same electrode, differing only in the concentration of one redox species. A concentration cell's potential, therefore, is determined only by the concentration difference of the particular redox species.
Consider the following voltaic cell:
Consider the following voltaic cell:
25.6K
01:14Model Approaches for Pharmacokinetic Data: Compartment Models
536
Compartmental analysis is a widely adopted approach to characterizing drug pharmacokinetics. It uses compartment models that conceptualize the body as a collection of reversibly communicating compartments, each representing a group of tissues exhibiting similar drug distribution characteristics. The movement rate of the drug between these compartments is typically described by first-order kinetics.
Two primary types of compartment models are recognized: mammillary and catenary. The more...
Two primary types of compartment models are recognized: mammillary and catenary. The more...
536
01:15Model Approaches for Pharmacokinetic Data: Physiological Models
250
Physiological models in pharmacokinetics are instrumental in understanding the distribution and elimination of drugs within the body. These models describe the drug concentration within target organs, influenced by factors such as drug uptake, tissue volume, and blood flow. Drug uptake is governed by the partition coefficient, which signifies the drug concentration ratio in tissue to that in the blood. The blood flow rate to a specific tissue is expressed as Qt, and the rate of change in tissue...
250
00:59Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
326
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...
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
326