Microscopy is a technique for capturing images of tiny objects, and it is an invaluable tool for investigating cells and tissues and their molecular constituents. Microscopy is particularly well-suited for assessment of cell, tissue, or organelle morphology; determination of macromolecule expression level, subcellular localization, translocation, or co-localization; and the measurement of cellular heterogeneity or the identification and study of cellular …
Physiologically Based Pharmacokinetic (PBPK) Modeling of Central Nervous System
by Marjory Moreau, Ph.D. I have worked in PBPK modeling for many years and until a few months ago, I never had to deal with the brain compartment. Well, I had a brain compartment in several of my models, but I never really thought about the blood brain barrier and all the transporters involved in protecting or bringing compounds into the brain until recently. I …
The Frontier of Aerosol Safety Testing with In Vitro and in Silico Methods
by Scott Slattery In May and June of this year, the annual Webinar Series on Inhalation Toxicity Testing was co-hosted by The US EPA, the PETA Science Consortium International, Syngenta, and Unilever. The nine webinars presented over three days provided an excellent look at current progress in the area of non-animal inhalation toxicity testing approaches. The talks covered the breadth of the field, addressing in …
Cardiac Toxicity Evaluation with a Human Tissue-Engineered Model
Dr. Kareen Coulombe joined us to share her latest findings for assessing cardiac toxicity using a predictive 3D human cardiac microtissue platform for assessing toxicity of chemical compounds. What you’ll learn: How NAM’s are used to assess cardiac toxicity How human 3-D cardiac microtissue systems can address limitations of traditional in vivo and in vitro assays in predicting arrhythmia generation …
Toward an Actionable Collaborative Data System for Toxicology
Patrick McMullen, Director of Computational Toxicology I have often joked that as a computational biologist in an applied field that has been slow to embrace bioinformatics, it is my goal to work myself out of a job. That is, if I can empower the scientific experts responsible for safety decisions with the right tools, then they can ask their questions …
Updated Guidance from OECD on Reporting PBPK Models for Risk Assessment
As an advocate in PBPK modeling for risk assessment, I want to share with you the latest guidance from the Organization of Economic Cooperation and Development (OECD). I write a lot of reports on PBPK models for clients, and it makes a huge difference to always use the same format to report the goal of the project, the development of the PBPK model and how it will be used. It makes my life easier and obviously the client appreciates being able to follow and understand …
Using Cells and Mathematical Models to Interpret Thyroid Hormone Disruption
by Jeff Fisher This story begins in 1998 when I reviewed a technical document for the chemical perchlorate, now known to be widely distributed in the environment on earth and has been found in high concentrations on Mars. In 1998, the subject of this document was a proposed safe drinking water level for perchlorate based on historic medical use of perchlorate as a probe of thyroid function, in the diagnostic called the thyroid discharge test. This document changed …
Advancing Neurotoxicity Screening of Environmental Compounds for Public Health Protection
Mamta Behl, M.S, Ph.D, D.A.B.T, explores the latest developments in neurotoxicity models. This method uses a combination of in vitro, in vivo extrapolation, and exposure assessment to rapidly screen compounds with neurotoxic potential and disseminate information in a timely manner for public health. What you’ll learn: A survey of the promising in vitro neurotoxic models How well these models have performed Use …
Using Short-term In Life Transcriptomic Studies to More Effectively Assess Dose Responses and Modes of Action
In the past, dose responses results from in life toxicology studies were used to estimate no observed effect levels (NOELs) and more recently benchmark doses (BMDs). These observational studies of apical endpoints were frequently followed up by mechanistic studies both in intact animals and in in vitro models to determine modes of action (MOAs) and lend support to using either linear or threshold-based low dose extrapolations. Over the past two decades, gene expression analysis …