October 29, 2021
Please join us for our next webinar on November 9 at 11am ET by Dr. Kannan Krishnan, Chief of the Air and Site Assessment and Climate indicators Branch (ASACIB) at the Office of Environmental Health Hazard Assessment (OEHHA) of California Environmental Protection Agency. He will take us through the journey of his lab’s work on chemical structure-property relationships for PBPK modeling – filled with ground-breaking findings, failures punctuated by lessons learnt and ideas for moving forward. What you’ll learn:
- Usefulness, limitations and possible future directions regarding the approaches based on chemical structure, molecular properties, and physicochemical properties to parameterize PBPK models for organic chemicals.
- Concepts and a framework for taking into account the uncertainty in the predictions of structure-property relationships in evaluating the level of confidence in PBPK models.
All registered participants will receive access to the webinar recording. We look forward to hosting you!
About our Speaker:
Dr. Kannan Krishnan is Chief of the Air and Site Assessment and Climate Indicators Branch (ASACIB) at the Office of Environmental Health Hazard Assessment (OEHHA) of California Environmental Protection Agency. He obtained his Ph.D. (Community health, specialization: Environmental Toxicology) from the University of Montreal, Canada. He is a Board-certified toxicologist (DABT), Fellow of the Canadian Academy of Health Sciences (FCAHS) and Fellow of the Academy of Toxicological Sciences (FATS). Kannan has authored or co-authored more than 200 publications and assumed the editorial role for 5 books and journal monographs related to PBPK modeling, mixtures toxicology, biomonitoring, quantitative structure-property relationship modeling, threshold of toxicological concern, and extrapolation methods (route to route, interspecies, intraspecies, and population-level) for health risk assessments. Over the years, he occupied leadership, managerial and strategic roles in non-profit research organization (Chief Scientific Officer & Director of Research Directorate at IRSST, Montreal, Canada), private sector (Risk Sciences International Inc., Ottawa, Canada) as well as academia (Chairman of the Department of Occupational and Environmental Health & Vice-Dean of Research at the School of Public Health of the University of Montreal). Kannan and his coworkers received 42 awards and peer-recognitions for their contributions, including the Paper of the Year Award from the Occupational and Public Health Specialty Section of the Society of Toxicology, 2018); Award for Best Publication in Toxicological Sciences, the official journal of the Society of Toxicology (2003); as well as the Science & Technological Achievement Award of the U.S. Environmental Protection Agency (Level II, 2009).
Abstract:
Physiologically-based pharmacokinetic (PBPK) models are useful tools for simulating the tissue and blood concentrations of the toxic moiety of chemicals and drugs as a function of dose, route, species, individual characteristics and exposure scenario. The emerging new approach methods based on in vitro exposures require the companionship of PBPK models for the conduct of reliable in vitro to in vivo extrapolations. However, the development of PBPK models has not kept up with the current and emerging needs to characterize the kinetics of individual chemicals and mixtures as well as their metabolites. One option is to develop reliable animal-replacement approaches to predict the various input parameters required for PBPK modeling. This presentation will describe the thought process and progress made over the past 25+ years at the University of Montreal in using structure – property relationships to develop input parameters such as blood:air partition coefficient (Pba), tissue:air partition coefficient (Pta), tissue:blood partition coefficient (Ptb) and intrinsic metabolic clearance (CLint = Vmax/Km).
The lessons learnt are structured to inform us the about possible future directions to facilitate the expansion of the use of chemical structure, molecular properties, and physicochemical properties to parameterize PBPK models for organic chemicals, depending upon the end-use and extent of the precision required. The talk will conclude by illustrating the importance of evaluating the level of confidence in the PBPK models based on the uncertainty in the predictions of the structure-property relationships in conjunction with the sensitivity of the dose metrics simulated by the PBPK models. (This presentation does not reflect the policy or the position of OEHHA or CalEPA).
About ScitoVation:
ScitoVation helps clients assess chemical compound safety using innovative science, next-generation technology, and professional expertise. ScitoVation is known for partnership, flexibility, and proven success in its work to develop safer and more effective pharmaceuticals, food ingredients, agricultural chemicals, commodity chemicals and consumer products. A spin-off of the former The CIIT and The Hammer Institutes for Chemical & Drug Safety Sciences, ScitoVation is an industry leader of New Approach Methods (NAMS) for chemical/drug discovery & development in the rapidly evolving global regulatory landscape.