In this presentation, Dr. Zhoumeng Lin introduces how we develop physiologically based pharmacokinetic (PBPK) models of drugs, environmental chemicals and nanoparticles for applications in nanomedicine, food safety, and human health risk assessments. He presents his recent studies to illustrate each application. Dr. Zhoumeng Linalso introduces a new physiological parameter database for PBPK modeling in food-producing animals, including cattle, swine, sheep, …
Upcoming Book Release: Clinical Pharmacology during Pregnancy, second edition, September 24, 2021
by Jeff Fisher Edited by Donald Mattison Lee-Ann Halbert I was the senior author of one chapter in the newly released textbook, “Clinical Pharmacology During Pregnancy, second edition.” Coauthors on the original research publications include scientists from the US FDA, Duke University, and Proctor & Gamble Corporation. The editors were Dr Donald Mattison and Ms. Lee-Ann Halbert. Dr Mattison, a physician/researcher has been a strong advocate of computational methods in the field of toxicology throughout his distinguished career with a focus …
The Importance of using Kinetically Derived Maximum Dose (KMD)
KMD allows for design of in-life experiments that are not confounded by non-linear effects, including saturation of absorption processes. This results in a data package that is more easily interpreted because of its increased relevance to human exposures. by Jeff Fisher For those who design repeated dose, subchronic and chronic animal toxicity studies, this concept may be an additional responsibility for you. Gone are …
Discovery of a new mechanism for genetic change: Exitron splicing implications for carcinogenesis
by Michael Black Carcinogenesis, or the process of transformation of cells to a cancerous state, often is associated with aberrations in messenger RNA splicing. Removal of introns in pre-mRNA is an essential step in normal cell processing of mRNA prior to transcription of a peptide from a final mRNA transcript. Alternative splicing of pre-mRNA gives cells the ability to regulate multiple final mRNA products from a single gene, adding diversity to the …
Development of a Molecular Fingerprint for Predicting Drug-induced Cholestasis
Jake Reske, ScitoVation graduate intern in toxicogenomics, will explains a meta-analysis strategy used to develop a preliminary classifier of hepatic cholestasis through public transcriptomic data sets. Cholestasis is a hepatic disease that results from bile acid metabolic dysregulation. We describe our approach to using transcriptomics, statistical modeling, and machine learning to identify molecular signatures of cholestasis. What you’ll learn: Data-driven approaches to identify …
New Approach Methodologies for Environmental Cardiotoxicity Testing
by Marjory Moreau Recently I attended a webinar on “Cardiac toxicity Evaluation with a human tissue-engineered model” by Kareen Coulombe, professor at Brown University. I am still blown away every time I hear Dr. Coulombe speak on this subject. In addition to being an excellent speaker, the work she and her team are doing is incredible. I recently wrote a blog on the brain and all its complexity because the brain is not an organ I had worked …
The Need for Increased Maturity in the Risk Assessment Ecosystem
by Dr. Jean Orelien Last year, the US EPA declared they would phase away from animal testing by 2035. Reaching this milestone will require the maturity of the risk assessment ecosystem. By maturity, I mean new roles need to be assumed along with improved interactions and (stronger) bonds within and between group as well as new entities. In this post, I share a …
Exploring In Vitro 3D Liver Models: Complexity Demands Different Needs
by Aarati Ranade Every time we perform an experiment with hepatocytes, I am curious to see how the culture looks over time after plating the cells. I carefully place the cell culture plate under the microscope. I carefully observe through the microscope eyepiece. The transition from round cells to formation of flat, hexagonal cells with one or two prominent nuclei with cell borders nicely touching each other to form a carpet-like monolayer …
Toward More Efficient Safety Testing Through Development of an Internal Threshold of Toxicological Concern
by Alina Y. Efremenko One of my memorable moments when I was a teenager was my family’s trip to the Grand Canyon. That was my first experience riding a horse. I begged my grandfather to come with me, and reluctantly he agreed. I asked him why he disliked the idea so much and he said, “No one asked the horses.” …
My Summer Internship with ScitoVation
by Gustavo Nativio Hey there! I‘m the resident intern here at ScitoVation for the summer. As someone deeply interested in systems biology and solving biological problems using mathematics and computational models, the work done by ScitoVation is fascinating to me. ScitoVation is using innovative computational modeling of physiological systems to improve regulation efficiency in the pharmaceutical industry and in the environmental health field! I work with Physiologically Based Pharmacokinetic (PBPK) modeling. PBPK modeling is a tool to predict the distribution and fate of drugs within an organism. PBPK …
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 …
What are NAMs?
by Sage Corzine If you got pumped up about NAMs in a toxicology webinar, tried to find more information on Google, and got redirected to the North American Menopause Society, you are not alone. NAMs or New Approach Methodologies are a vital and growing part of chemical hazard and risk assessment research. Here are a few fun facts …
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 …
Why ScitoVation is Part of my Journey
Dr. Jean Orelien, CEO My passion is helping solve problems at the intersection of health, science, and technology. In other words, problems for which we can use science and technology to improve lives. With ScitoVation, our long-term vision is to achieve this by helping our clients develop safe chemicals for humans and the environment using innovative science and technology. There are parallels between our work at ScitoVation and SciMetrika, the first company I founded in 2004 and sold in 2018. At SciMetrika, we used …
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 …
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 …
Guidelines for assessing Pharmacokinetic Bias in Epidemiology
Melvin E. Andersen Biomarkers of exposure can be measured at lower and lower levels due to advances in analytical chemistry. Using these highly sensitive methods, some epidemiology studies report associations between plasma and urinary biomarkers and health outcomes at biomarker levels much below those associated with effects in animal studies. In some cases, these associations may arise from pharmacokinetic (PK) bias, i.e., a situation where a confounding …
Better alternative models for risk assessment: In vitro inhalation toxicity assay and dosimetry modeling
Last week, my colleague, Scott Slattery, presented a webinar on in vitro inhalation point-of-contact toxicity testing with vapors. It brought me back to when I started working with Scott last year on this project. As a physiologically based pharmacokinetic modeler, the only time I worked in a lab…
New publication investigating mode of action for high-dose effects of 4-methylimidazole
by Patrick McMullen We are pleased to announce our most recent manuscript, A systematic approach to evaluate plausible modes of actions for mouse lung tumors in mice exposed to 4-methylimidazole, published in Regulatory Toxicology and Pharmacology. 4-methylimidazole is a ubiquitous compound present in foods that undergo thermal browning (i.e., Maillard reaction) processes. The work described here—a combined effort of investigators from ScitoVation and ToxStrategies supported by the American Beverage Association—aimed …