Continuing Education


The Continuing Education (CE) Program offers a wide range of courses that cover established knowledge and new developments in toxicology and related disciplines.

  • Earn CE credit for professional certification and licensing.
  • Expand your knowledge of novel concepts and methods.
  • Learn from an array of regulatory, industry, and academic perspectives.
  • Receive CE course materials digitally weeks before the course.
In the center of the image is a woman sitting at a long table. She has a laptop in front of her, but she is looking beyond the laptop. Around the woman, you can see other long tables where other people sit with laptops.

Sunrise Minicourse

Taking place from 7:00 am to 7:45 am, this special Continuing Education minicourse includes breakfast and features three speakers.

Sunday, 7:00 AM to 7:45 AM

SR01

An Introduction to Clinical and Medical Toxicology

This course will introduce the participants to the basics of the field and to the tools, new and old, that may be used by clinical toxicologists.

Chair(s):
John Benitez, State of Tennessee Department of Health; and William Mattes, Independent Consultant.
Primary Endorser:
Clinical and Translational Toxicology Specialty Section

While all toxicology addresses the adverse effects of agents on living organisms, clinical and medical toxicology has a unique role not often encountered in traditional toxicology practice or research. Clinical and medical toxicology are focused on the immediate needs of patients suspected of being poisoned. It requires an in-depth knowledge of both diseases and their etiology, as well as the effects of potential poisons, to be used in differential diagnosis. A clinical or medical toxicologist must consider three points: the substance involved, the toxic response, and the mechanism by which it occurs to determine the best treatment options for the patient. This course will introduce the participants to the basics of the field, and introduce the tools, new and old, that may be used by the clinical toxicologist.

Affecting Patient Care—What Are Clinical and Medical Toxicologists? John Benitez and Nena Bowman, State of Tennessee Department of Health, Nashville, TN.

Analytical Detection of Drug Exposure in the Clinical Laboratory: Embracing Novel Technologies and Alternative Matrices. Kara Lynch, University of California San Fransisco, San Fransisco, CA.

Continuing Education Courses

These courses take place on Sunday, March 19. They are the only Scientific Sessions presented on Sunday and are available for an added fee. There are six courses in the morning, 8:15 am-12:00 Noon, and six courses in the afternoon, 1:15 pm–5:00 pm.

  • Morning AM MAR 19 2023
  • Afternoon PM MAR 19 2023
Sunday, 8:15 AM to 12:00 Noon

AM02

A Training on the OECD Guidance for Characterizing, Validating, and Reporting Physiologically Based Kinetic Models

Attendees enrolled in this course will learn about the fundamental concepts underlying PBK modeling, data needs during model development, and commonly used metrics for model evaluation.

Chair(s):
Cecilia Tan, US EPA; and Alicia Paini, esqLABS GmbH, Germany.
Primary Endorser:
Biological Modeling Specialty Section
Other Endorser(s):
Risk Assessment Specialty Section; Women in Toxicology Special Interest Group

Physiologically based kinetic (PBK) modeling is a scientifically sound tool for predicting internal dose metrics by describing the critical physiological, physicochemical, and biochemical processes that determine the disposition of a chemical in an organism. Here, a general term kinetic is used as synonymous with pharmacokinetic (PK), toxicokinetic (TK), or biokinetic (BK). Traditionally, in environmental toxicology, the calibration of parameters in a PBK model and the evaluation of its predictive capability rely heavily on comparing model simulations with in vivo blood or tissue concentration data obtained in laboratory animals. However, the availability of in vivo data is limited to well-studied chemicals, which impedes the broader applications of PBK models by regulatory agencies. The recent paradigm shift towards using new approach methodologies (NAMs) for chemical risk assessment necessitates the use of PBK models, developed and evaluated without data from live animals, to convert a bioactive concentration observed in cell-based toxicity assays to an equivalent human exposure level. To keep pace with the global efforts to develop and incorporate NAMs in chemical risk assessments, the Organisation for Economic Co-operation and Development (OECD) published a guidance document (GD), in 2021, on characterizing, validating, and reporting PBK models without the use of animal data. This GD includes contextual information of the process to characterize and evaluate a PBK model in a regulatory context; and highlights common in vitro and in silico approaches to parameterize a model. Characterized in a modelling assessment framework, the OECD GD provides a model reporting template and a model evaluation checklist for evaluating the credibility of PBK models for their intended purposes. Adoption of the OECD PBK model GD is now encouraged when developing an OECD Integrated Approaches to Testing and Assessment (IATA). This course is the first time a training is offered following the key principles laid down in the OECD GD. After a brief overview of the guidance, two speakers will highlight commonly used, modern in vitro and in silico approaches for parameterizing a PBK model, as described in the second chapter of the GD. Next, two other speakers will present the various tools, recommended in the third chapter of the GD, for evaluating the context, implementation, and scientific validity of a PBK model without using in vivo data. At the end of the course, a hands-on exercise will give the attendees, both newcomers and experts, an opportunity to apply their knowledge in evaluating example PBK packages. This course is designed for those who are involved in developing, applying, and promoting the acceptance of PBK models; and those who seek to reduce/replace animal testing and incorporate more predictive mechanistic data in chemical risk assessment for human, animal, and environmental health. Attendees enrolled in this course will learn about the fundamental concepts underlying PBK modeling, data needs during model development, and commonly used metrics for model evaluation. These topics will be applicable to PBK models developed for drugs, industrial chemicals, biocides, pesticides, food additives, as well as chemicals in cosmetics and consumer products. These topics are also applicable to models developed for humans, laboratory test species, farm animals, and species of ecological relevance.

An International Effort to Promote the Regulatory Use of PBK Models: Introduction to the OECD PBK Guidance. Cecilia Tan, US EPA, Research Triangle Park, NC.

PBK Modeling Parameterization Using In Vitro Methods and Read-Across Workflow. Alicia Paini, esqLABS GmbH, Saterland, Germany.

Applying In Silico Methods for Model Parameterization. Michael Lawless, Simulations Plus, Lancaster, CA.

PBK Modeling Assessment Framework for Model Reporting and Evaluation. Bette Meek, University of Ottawa, Ottawa, ON, Canada.

Uncertainty and Sensitivity Analyses for PBK Modeling Evaluation. Frederic Y. Bois, Certara UK Limited, Sheffield, United Kingdom.

Hands-On Model Evaluation.All Speakers.

Sunday, 8:15 AM to 12:00 Noon

AM03

Advanced Discovery Toxicology: Integrating Toxicology with Other Functions on the Team

Overall, this course will inform toxicologists of new insights to utilize multidisciplinary tools to develop proactive safety paradigms that could reduce project delays and late-stage drug attrition.

Chair(s):
Satoko Kiyota, Genentech Inc.; and Marie Lemper, UCB S.A. Belgium.
Primary Endorser:
Drug Discovery Toxicology Specialty Section
Other Endorser(s):
Computational Toxicology Specialty Section; Mechanisms Specialty Section

The importance of having toxicologists fully integrated in early discovery project teams has become evident to enable efficient strategic decision-making around lead candidate selection. Last year, Drug Discovery Toxicology Specialty Section hosted the Continuing Education (CE) course to focus on an overview of the drug discovery toxicology: from target assessment to identification of drug candidates. This year, the aim of this CE course is to provide an opportunity for toxicologists to gain insights into nonstandard toxicology contents (medicinal chemistry, ADME/pharmacokinetics, formulation development, and machine-learning) which can significantly impact safety outcomes and design of nonclinical safety strategies in the small molecule discovery space. The first speaker will focus on the link of medicinal chemistry and safety liabilities. While the concept that chemical structures and physicochemical properties can drive safety liabilities has been well recognized, toxicologists with limited professional training in medicinal chemistry may not feel empowered to influence medicinal chemistry design. This presentation will help toxicologists gain valuable insights into medicinal chemistry approaches to mitigate potential toxicophores and help identify a chemical series with high potential. The second speaker will discuss key in vitro ADME properties and liabilities, which can increase toxicity risks in vivo. Additional focus will include how predicted pharmacokinetic profiles in human can enable efficient compound triage from a safety perspective before progressing to in vivo toxicity assessments. The third and fourth speakers will focus on interspecies metabolite comparison and formulation development, which are essential components in the design and conduct of nonclinical in vivo toxicity assessments. To ensure the toxicology data from nonclinical species are meaningful for hazard identification and human risk assessment, the selected species should be relevant to human for not only primary pharmacology but also metabolite profile. Additionally, robust exposure should be demonstrated to ensure proper toxicological assessments, especially for non-oncology indications. Proper formulation selection is fundamental to address challenging properties of a compound and enable in vivo evaluation with desired exposure levels. Our last speaker will discuss how the emergence of machine-learning can enable off-target hypothesis generation for an unexpected toxicity observed in vivo. Toxicologists should ideally promptly identify a cause of unexpected toxicities and propose model(s) to screen out compounds with an unfavorable profile if it is off-target-mediated. However, regardless of considerable time and financial investments, discovering the mechanism of toxicity may not be possible by empirical methods alone. Machine learning may help to accelerate generating testable hypotheses. The course will conclude with an interactive session to focus on how toxicologists can efficiently gain diverse ranges of scientific expertise and influence better decision-making early in the discovery stage. Overall, this course will inform toxicologists of new insights to utilize multidisciplinary tools to develop proactive safety paradigms that could reduce project delays and late-stage drug attrition. These concepts and approaches are generally applicable for predictive safety and investigative toxicology in any field, including academic research work.

Overview of Cross-Functional Aspects of Toxicologists in Drug Development. Dinah Misner, Aligos Therapeutics Inc., South San Francisco, CA.

Making Sense of the Bonds between Chemistry and Toxicology. Graham Smith, AstraZeneca, Cambridge, MA.

Toxicity Prediction from a DMPK Aspect in Drug Discovery. Tomoya Yukawa, Takeda Pharmaceutical Company Limited, Kanagawa, Japan.

A Pragmatic Approach in Utilizing In Vitro Metabolite Identification for Species Selection. Jonathan Maher, Pliant Therapeutics Inc., South San Francisco, CA.

Formulation Fundamentals: From Theory to Practice. Vijay Sethuraman, Genentech Inc., South San Francisco, CA.

Machine-Learning to Enable Off-Target Hypotheses Generation. Yuan Wang, UCB S.A. Belgium, Cambridge, MA.

Interactive Session: How to Efficiently Anchor “Non-toxicology” Discussions to Toxicology. Marie Lemper, UCB S.A. Belgium, Cambridge, MA.

Sunday, 8:15 AM to 12:00 Noon

AM04

Beyond the Powerhouse: Investigating Mechanisms of Mitotoxicity

Following the course, attendees will have a clear understanding of the highly dynamic roles mitochondria play within the cell and at tissue and organismal level and the challenges and current solutions to analysis of mitochondrial endpoints, as well as a new perspective on the role of mitochondria in toxicological mechanisms.

Chair(s):
Katherine Morton, Duke University; and Yvonne Will, Janssen: Pharmaceutical Companies of Johnson & Johnson.
Primary Endorser:
Molecular and Systems Biology Specialty Section
Other Endorser(s):
Mechanisms Specialty Section; Women in Toxicology Special Interest Group

Mitochondria are the central energy producing organelle in the cells of most eukaryotes, though their roles within the cell expand far beyond bioenergetics. Recent work shows that this dynamic organelle serves as a regulator of apoptosis, oxidative stress, calcium homeostasis, signal transduction, steroid hormone synthesis, and immunity among other pathways. As a result, mitochondria can alter cell and tissue function leading to aging, neurodegenerative disease, cardiovascular disease, inflammatory disorders, and increased cancer severity. However, despite the increasing investigations into the non-bioenergetic roles of mitochondria, these areas remain critically understudied and misunderstood. For example, mitochondrial iron uptake plays a critical role in iron homeostasis and related hepatotoxicity. Similarly, mitochondrial dysfunction is increasingly identified as a key factor in Gulf War Illness, suggesting newfound roles in other diseases. This Continuing Education course will explore the wide roles mitochondria play in response to cellular stress and xenobiotics beyond bioenergetic alterations, and to challenge how researchers traditionally examine and include mitochondrial toxicology in their work. Speakers with expertise in mechanisms and assessment of mitochondrial toxicity will present (1) an introduction to mitochondrial toxicity focusing on the need to examine specific mechanisms of toxicity within mitochondria to understand the resultant adverse outcomes; three case studies displaying the methods used and mechanisms of mitochondrial toxicity that extend beyond alterations to bioenergetics including (2) mitochondrial iron homeostasis and its role in acetaminophen hepatotoxicity, (3) antiviral medication induced alterations to heart epigenetic and metabolic landscapes, and (4) the role of mitochondria in function of the innate immune system and inflammation. Next, we will progress from in-depth mitochondrial mechanisms to how this knowledge can be applied by using (5) mitochondria as biomarkers for renal exposures. Finally, in a world with an ever expanding need for toxicological assessment of new drugs, toxins, and toxicants, we will explore (6) how mitochondrial testing has been improved and conducted in large Pharma and (7) how large Pharma is upscaling mitochondrial toxicity testing to meet increasing demand in the future.

Following the session, attendees will have a clear understanding of the highly dynamic roles mitochondria play within the cell and at tissue and organismal level, the challenges and current solutions to analysis of mitochondrial endpoints, and a new perspective on the role of mitochondria in toxicological mechanisms. Further, they will be empowered to assess how these less understood mitochondrial mechanisms may play key roles in their own work, ultimately expanding and improving toxicological evaluations.

Mechanisms of Mitochondrial Toxicity. Joel Meyer, Duke University, Durham, NC.

Mitochondrial Iron Uptake and Release Pathways: Their Role in Cytotoxicity. Anna-Liisa Nieminen, Medical University of South Carolina, Charleston, SC.

Long-Term Cardiac Effects of Developmental Exposure to Antiretrovirals. Janine Santos, NIEHS/NTP, Research Triangle Park, NC.

Mitochondrial Control of Innate Immunity and Inflammation: Implications for Human Disease. A. Phillip West, Texas A&M University, College Station, TX.

Renal Mitochondria as Sentinels for Exposures to Environmental Toxicants and Nephrotoxic Drugs. Lawrence Lash, Wayne State University, Detroit, MI.

Two Decades of Mitochondrial Toxicity Testing in Large Pharma. Yvonne Will, Janssen: Pharmaceutical Companies of Johnson & Johnson, San Diego, CA.

Upscaling Mitochondrial Toxicity Testing in Large Pharma. Natalie Mesens, Janssen: Pharmaceutical Companies of Johnson & Johnson, San Diego, CA.

Sunday, 8:15 AM to 12:00 Noon

AM05

Non-traditional In Vivo Animal Models in Developmental, Reproductive, and Juvenile Toxicology

Traditionally, rats, mice, and rabbits have been used as preferred animal models (rodent and nonrodent) for nonclinical developmental, reproductive, and juvenile toxicity testing. Published regulatory guidelines recommend the selection of relevant animal models, based on individual project requirements, that may be influenced by systemic exposure and prior systemic toxicity data from general toxicology studies.

Course Book

Room:
CC Ballroom ?
Chair(s):
Caren Villano, Boehringer Ingelheim Pharmaceuticals Inc.; and Edward Marsden, Charles River, France.
Primary Endorser:
? Specialty Section
Other Endorser(s):
Reproductive and Developmental Toxicology Specialty Section

Traditionally, rats, mice, and rabbits have been used as preferred animal models (rodent and nonrodent) for nonclinical developmental, reproductive, and juvenile toxicity testing. Published regulatory guidelines recommend the selection of relevant animal models, based on individual project requirements, that may be influenced by systemic exposure and prior systemic toxicity data from general toxicology studies. For the majority of compounds, the traditional models are quite effective and widely accepted by international health authorities. Species-specific dose-limiting toxicity, differences in metabolism across test species, and pharmacological relevance may require researchers to investigate non-traditional models including guinea pigs, mini-pigs, and dogs. In addition, certain pharmacological classes (e.g., antibiotics in rabbits) or chemistries may also limit the use of the traditional models. Further, in the last year, during the COVID-19 pandemic, a severe shortage of nonhuman primates (particularly sexually mature females needed for ePPND studies) has also shifted the focus towards non-traditional animal models. This CE course will walk participants through the various considerations for study designs as well as pros and cons of some of the more commonly used non-traditional mammalian models in DART and juvenile toxicity testing. It will also touch upon the use of rabbits and their limitations in fertility and juvenile animal studies. The first presentation will describe how collaboration between animal model suppliers, industry, and academia has driven scientific development and expanded the use of the Göttingen Minipig into DART and juvenile toxicology, with specific projects highlighted. The second presentation will focus on the use of Beagle dogs in developmental and juvenile toxicity testing including many critical aspects of study design, associated species differences, and terminology. The third presentation will explore the scientific considerations for selection of alternatives to nonhuman primates to address embryo-fetal risk and provide examples of how transgenic, knock-in, and knock-out animal models and surrogate molecules can be used to support the nonclinical hazard assessment for various biotherapeutics. The course will wrap up with a summary of the current regulatory guidance on DART and juvenile animal toxicity testing which include discussion of the use of non-traditional species or models. At the end of this course, participants will be familiar with a variety of approaches to assessing embryo-fetal risk and juvenile toxicity in animal models not commonly used in DART as well as the current regulatory guidance supporting them.

Introduction to Non-traditional Models for use in DART and Juvenile Toxicology. Caren Villano, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT.

Scientific Development of the Göttingen Minipig in DART and Juvenile Toxicology: Collaborations and Joint Efforts. Lars Mikkelsen, LarSolution, Frederiksberg, Denmark.

Use of Beagle Dogs in DART and Juvenile Toxicology. Stephanie Clubb, Charles River, Edinburgh, United Kingdom.

Use of Alternate Models (KO/KI Models, Surrogates, Disease Models) in DART and Juvenile Toxicology. Alan Hoberman, Charles River, Horsham, PA.

Regulatory Guidance on the Use of Non-traditional Species in DART and Juvenile Toxicology. David Klein, US FDA, Silver Spring, MD.

Sunday, 8:15 AM to 12:00 Noon

AM06

Tools Supporting Open Chemical Evaluations

This session will provide attendees with an understanding of open-source—often web-based—tools and resources that can be applied in a context-specific manner for understanding chemical-biological interactions and informing chemical assessments.

Chair(s):
David Reif, North Carolina State University; and Shannon Bell, RTI International.
Primary Endorser:
Regulatory and Safety Evaluation Specialty Section
Other Endorser(s):
Computational Toxicology Specialty Section; Risk Assessment Specialty Section

The rapid expansion of computational and in vitro methods for the analysis of chemical-biological interactions has brought with it a wealth of open-source tools and resources that enable discovery and analysis. This has supported the increased use of these resources to support finding and generating information for prioritization, study waivers, weight of evidence, or other regulatory applications and aiding in chemical assessments. Many of these new tools are open access and web-based which has enabled broader access.

This session will provide attendees with an understanding of open-source and often web-based tools and resources that can be applied in a context-specific manner for understanding chemical-biological interactions and informing chemical assessments. We will open with an overview of regulatory testing strategies that incorporate the use of nonanimal methods to provide a background for how the tools and resources discussed can be used. The next three presentations will provide an overview of resources that contain traditional and NAMs testing data as well as tools that support the assessment needs. Case studies will be used to allow participants to “follow along” or they can work through the course material at their leisure. These presentations will address: how can we find existing data for a given chemical or chemicals that are strcturally similar, determine if existing data be used to fill in gaps, and how can computational models be leveraged to generate predictions that add to the weight of evidence? Our final presentation will highlight some new tools and opportunities to derive narratives of chemical-biological interactions. Together these presentations are intended to inform participants on resources available and provide a practical guide on when or how to use them. Objectives: Introduce participants to the mechanisms in which nonanimal approaches can be used to support assessments. Highlight resources for access to data and tools that enable the following applications; waivers; read-across; defined approaches and integrated approaches to testing and assessments (IATA); and QSAR-based modeling. Showcase new resources to complement narratives.

Creating a Narrative for Chemical Effects Using NAMs. Shannon Bell, RTI International, Durham, NC.

National Toxicology Program Tools to Support, Identify, and Explore Data. Scott Auerbach, NIEHS/NTP, Research Triangle Park, NC.

Supporting Chemical Evaluations Using Transparent and Accessible Data. Nisha Sipes, US EPA, Research Triangle Park, NC.

Supporting Chemical Hazard Assessments Using the OECD QSAR Toolbox. Andrea Gissi, European Chemicals Agency, Helsinki, Finland.

Omic-based Tools to Support Chemical Evaluations. Jessica Ewald, McGill University, Montréal, QC, Canada.

Wrap-Up and Synthesis. David Reif, North Carolina State University, Raleigh, NC.

Sunday, 8:15 AM to 12:00 Noon

AM07

Unique Applications of Systematic Review Methods: Assessment of Ecotoxicity, Environmental Fate, Exposure, Mechanisms, and Comparison of Test Methods

Building on courses from previous years, this session seeks to provide members with a brief overview of systematic review (SR) methods and principles followed by analyses of how these methods can be applied or adapted to information beyond traditional human health hazard endpoints (e.g., epidemiology and anmal toxicity study evaluating apical endpoints).

Chair(s):
Kelly Salinas, SRC Inc.; and Marc Stifelman, US EPA.
Primary Endorser:
Risk Assessment Specialty Section
Other Endorser(s):
Hispanic Organization of Toxicologists Special Interest Group; Women in Toxicology Special Interest Group

Building on courses from previous years, this session seeks to provide members with a brief overview of systematic review (SR) methods and principles followed by analyses of how these methods can be applied or adapted to information beyond traditional human health hazard endpoints (e.g., epidemiology and anmal toxicity study evaluating apical endpoints). SR methods have been implemented to evaluate data streams using unbiased, reproducible, and transparent approaches. The application to a broader base of evidence is very important in the practice of risk assessment, given that assessment conclusions are collectively informed by exposure characterization as well as ecological receptors.

The course is outlined as follows. The first talk will provide a brief review of SR principles followed by an overview of the translation of principles and techniques of SR across diverse disciplines (i.e., ecotoxicity, environmental fate, exposure, mechanistic, and in vitro/in vivo toxicity testing data). The remaining talks will address the unique aspects and challenges of application of SR to these specific disciplines.

The second speaker will discuss how ECOTOXicology Knowledgebase (ECOTOX) literature review and data curation protocols, while ECOTOX-specific, were designed to align with SR methods. Methods were developed to ensure that ecotoxicity data were extracted in sufficient detail to support independent evaluation, synthesis, and/or review of ECOTOX data documents ranging from scoping documents to regulatory decision-making.

The focus of the third presentation will be the application of SR methods to environmental fate endpoints, and how the systematic evaluation of these endpoints influences prioritization, assessment, and prediction of human health and ecological hazard and toxicity. The development of a “fit-for-purpose evaluation framework” to systematically assess data unique to environmental fate endpoints, including field/monitoring data and data estimated from environmental fate and transport models will be described.

The fourth presentation will focus on the application and validation of SR methods to environmental exposure data, specifically data needed to estimate daily soil ingestion rates in humans. The application of SR principles, including the development of a Population, Exposure, Comparator, and Outcome (PECO) statement specific to the soil ingestion of contaminants, will be presented.

The fifth speaker will discuss challenges associated with using SR principles in the synthesis and integration of mechanistic data. Adjustments of SR methods needed to evaluate mechanistic data, including a definition of the objective/scope of the use of the data and selection/refinement of an appropriate critical appraisal tool for various types of mechanistic data (e.g., in silico, in vitro, in vivo, and epidemiological data), will be presented. Case studies will be used to demonstrate that these SR adjustments rely on knowledge of standard constructs and methods used in toxicology and/or risk assessment.

The final speaker will discuss evidence-based methods used to assess the correlation of in vitro data (from ToxCast) and in vivo data (from standard toxicity studies and human clinical trials) to predict human health hazard. A case study will be presented to show how data from these streams were evaluated systematically to predict the effects associated with two antidiabetic drugs in humans.

Taken together, this CE course will demonstrate how SR methods, which are well developed to evaluate human health toxicity studies, are being applied to other data streams. The audience will be provided with a working knowledge base to assess diverse endpoints using SR methods. This course will appeal to audience members of diverse backgrounds and toxicological disciplines who are interested in learning about and applying SR methods, including scientists who are developing/conducting studies (related to ecotoxicity, environmental fate, exposure, mechanistic, in vitro/in vivo toxicity testing, and others), risk assessment practitioners, and regulators.

Background on Systematic Review: Principles, Methods, and Applications. Kris Thayer, US EPA/CPHEA, Research Triangle Park, NC.

Application of Systematic Review Principles to Ecotoxicity Studies: ECOTOXicology Knowledgebase. Jennifer Olker, US EPA/CCTE, Duluth, MN.

Systematic Review Principles Applied to Environmental Fate. Mary Kawa, SRC Inc., North Syracuse, NY.

Application of Systematic Review Principles and Components to Estimate Daily Soil Ingestion Rates for Humans. Marc Stifelman, US EPA, Seattle, WA.

Tailoring Off-the-Shelf Systematic Review Methods to the Identification and Evaluation of Mechanistic Data. Daniele Wikoff, ToxStrategies Inc., Asheville, NC.

Using Evidence-Based Approaches to Compare Toxicological Test Methods: A Case Study Using Troglitazone and Rosiglitazone. Katya Tsaioun, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.

Sunday, 1:15 PM to 5:00 PM

PM08

Checking In on Adverse Outcome Pathways: Evolving Development, Evaluation, and Application

Following the course, participants will be familiar with the most recent developments in best practices to support AOP development, assessment, and application, as well as evolving supportive resources within the OECD program.

Chair(s):
Kristie Sullivan, Physicians Committee for Responsible Medicine; and Bette Meek, University of Ottawa, Canada.
Primary Endorser:
In Vitro and Alternative Methods Specialty Section
Other Endorser(s):
Computational Toxicology Specialty Section; Risk Assessment Specialty Section

Adverse outcome pathways (AOPs) provide convenient integrating organizational constructs for assembling and evaluating mechanistic information at different levels of biological organization in a form designed to support a range of regulatory applications. These include the development of integrated approaches to testing and assessment (IATA) and chemical specific assessment to inform predictive inference and mode-of-action (MOA) analysis. There has been much experience gained in the last ten years, since the introduction of the AOP development program by the Organization for Economic Co-operation and Development (OECD)—and in the more than five years since a similar course was offered to Society of Toxicology members. Guidance and an associated handbook supports developers in the description and evaluation of AOPs via a publicly available knowledgebase. The program also includes formal peer engagement in the form of coaching for AOP development, external scientific review, and endorsement by parent OECD committees on testing and assessment. Increasing experience in AOP development and application contributes to continuing evolution of the methodology to meet regulatory need. Areas of evolution include the more systematic consideration of supporting data, extension of qualitative weight of evidence considerations to quantitation of key event relationships, and increasing experience in application. This course builds on training developed within the OECD program on best practices of documentation and assessment, including updates to the AOP-Wiki to encourage the use of common ontologies and delineation of literature analysis strategies and factors that modulate quantitative relationships. Consideration of disease pathways associated with nonchemical stressors contributes also to expansion of evolving knowledge. The course includes practical demonstration of the Wiki/knowledgebase, tips for developers and assessors, and development and application examples. Each presentation will cover different aspects of AOP development and application and, using real examples, offer a comprehensive overall learning experience. The first presentation will update attendees on how the available guidance and tools for AOP development have evolved to reflect experience with increasing and expanding content and biological space. The second presentation will emphasize the importance of transparently and effectively documenting evidence collection and evaluation by sharing tools and best practices with prospective AOP authors and users. This will lead to a comprehensive demonstration of the AOP Wiki, including changes to the publicly available interface that will be of interest to prospective developers as well as those seeking to use AOP information already available. The rest of the course will transition into a discussion of current and future applications of AOPs, including for the development of IATAs, transitioning to next-generation risk assessment and decision-making with new approach methodologies (NAMs), through globally relevant application examples. Following the course, participants will be familiar with the most recent developments in best practices to support AOP development, assessment, and application, as well as evolving supportive resources within the OECD program.

Course Introduction and AOPs in Context. Kristie Sullivan, Physicians Committee for Responsible Medicine, Washington, DC.

The Evolution of Best Practices for the Development and Description of AOPs Suitable to Support Regulatory Application of New Approach Methodologies. Dan Villeneuve, US EPA, Duluth, MN.

Documenting Evidence Identification and Assessment to Support Regulatory Application. Bette Meek, University of Ottawa, Ottawa, ON, Canada.

Wiki Evolution and Demonstration. Stephen Edwards, RTI International, Research Triangle Park, NC.

Structuring Integrated Approaches to Testing and Assessment in the Presence and Absence of a Specific Mechanism/Relevant AOP. Gavin Maxwell, Unilever, Bedford, United Kingdom.

Case Studies on the Development and Use of AOPs at the European Food Safety Agency. Andrea Terron, European Food Safety Authority, Parma, Italy.

Sunday, 1:15 PM to 5:00 PM

PM09

Immunosafety: Current Considerations and Applications in the Landscape of Immunomodulatory Therapies

Immunosafety evaluation requires an understanding of the complex and dynamic nature of the immune system, therapy mechanism of action, effects within the context of disease, and other patient-related or clinical considerations.

Chair(s):
Tracey Papenfuss, StageBio; and Shermaine Mitchell-Ryan, HESI.
Primary Endorser:
Immunotoxicology Specialty Section
Other Endorser(s):
Comparative Toxicology, Pathology, and Veterinary Specialty Section

Over the last decade, there have been significant advancements in the development of therapies that affect or are specifically designed to target the immune system. Therapies designed to modulate the immune system are being used to treat cancer (immune-oncology), autoimmune diseases, and a wide array of inflammatory or other diseases having an immunopathogenic origin. Immunotoxicology studies the toxic effects of chemicals, drugs, or other xenobiotics on the immune system. However, with the development of a multitude of immunotherapies with nuanced immunomodulatory effects, there is an increasing need to understand immune-related effects that go beyond traditionally recognized toxicity. With such immunomodulatory therapies, it can be difficult to determine whether immune-related effects reflect therapeutic efficacy and on-target effects, represent exaggerated pharmacology, overt toxicity, or a combination of these effects. The term immunosafety has developed to reflect the integrated approach to evaluating immune system changes (beyond “toxic”) and the therapeutic or safety implications seen with immunomodulatory therapies. Immunosafety evaluation requires an understanding of the complex and dynamic nature of the immune system, therapy mechanism of action, effects within the context of disease, and other patient-related or clinical considerations. The first talk will provide an overview of immunosafety and toxicology considerations within the landscape of immunotherapies and the remaining talks will focus on providing information and practical considerations of immunopathology evaluation, comparative and species-specific concepts, clinical and translational considerations, regulatory considerations, and immunotoxicology assays important for immunosafety.

Immunosafety—History, Basic Background, and Toxicology Considerations in the Current Landscape of Immunomodulatory Therapies. Birgit Fogal, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT.

Pathology of the Immune System and Considerations for Immunosafety and Adversity Determination. Tracey Papenfuss, StageBio, Mount Jackson, VA.

Comparative and Species Considerations for Immunosafety. Ashwini Phadnis-Moghe, Takeda Pharmaceutical Company Limited, Cambridge, MA.

Clinical and Translational Considerations for Immunotherapies. Ashlyn Bassiri, Kriya Therapeutics, Durham, NC.

Immunotoxicology Evaluation: Tools and Strategies for Immunosafety. Marie-Soleil Piche, Charles River, Wilmington, MA.

Regulatory Considerations for Immunosafety. David McMillan, US FDA/CDER, Silver Spring, MD.

Sunday, 1:15 PM to 5:00 PM

PM10

In Vitro to In Vivo Extrapolation Strategy and Guidance across Organ System Toxicities

Based on gaps in IVIVE guidance, this Continuing Education course will explore successful IVIVE studies across research sectors and highlight important strategy and principles critical for regulatory consideration.

Chair(s):
Samantha Faber, Takeda Development Center Americas Inc.; and Helena Hogberg-Durdock, NIEHS.
Primary Endorser:
In Vitro and Alternative Methods Specialty Section
Other Endorser(s):
Clinical and Translational Toxicology Specialty Section; Regulatory and Safety Evaluation Specialty Section

In vitro to in vivo extrapolation (IVIVE) efforts are critical for addressing low concordance of preclinical animal models for chemical-induced human toxicity and aligning with global efforts to reduce, refine, or replace animal testing (3Rs). Notably, the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH), Toxicology in the 21st Century (Tox21), and other regulatory initiatives support the development of new approach methodologies (NAMs) and strategies to advance the field of IVIVE. As such, a wave of rationally designed in silico models, advanced in vitro systems, 'omics signatures (toxicogenomics, proteomics, epigenomics, metabolomics, and lipidomics), and physiological-based pharmacokinetic (PBPK) modeling approaches have been developed and demonstrate utility for IVIVE across diverse organ systems. Despite these advancements, understanding of key concepts related to robust NAM development, validation, and implementation within a regulatory framework to progress IVIVE adoption is limited. Based on gaps in IVIVE guidance, this continuing education course will explore successful IVIVE studies across research sectors and highlight important strategy and principles critical for regulatory consideration. Specifically, the course will focus on IVIVE strategy for prominent organ system toxicities including, inhalation toxicity, hepatotoxicity, developmental neurotoxicity, and cardiovascular toxicity. We will begin the course with an overview of IVIVE concepts and utility across academic, government, and industrial toxicological sectors. Our first speaker will highlight the value of IVIVE within the field of inhalation toxicity using IVIVE case studies that bridge the gap between inhalation exposure to complex mixtures in vitro and tobacco-free nicotine product human risk assessment. Next, speaker two will detail the use of toxicogenomics, PBPK modeling, and publicly available toxicological databases (e.g., TG-GATES) to assess drug-induced liver injury (DILI) IVIVE within a robust compound validation set and describe how these approaches can aid in de-risking hepatotoxicity across research sectors. Speaker three will focus on an integrated approach to testing and assessment (IATA) case study for developmental neurotoxicity (DNT) using a battery of NAMs to prioritize a class of compounds and how exposure data in humans can be used to interpret this data. Speaker four will provide a balanced viewpoint of the cardiovascular NAM landscape, including 2D and 3D cardiac and vascular toxicity model approaches, challenges, and strategies for IVIVE implementation. The final speaker will conclude the course with discussion of regulatory considerations and paths forward for adoption of IVIVE approaches within adverse outcome pathway (AOP) contexts and clinical packages. Focusing on critical organ systems, this course will provide guidance surrounding pertinent assay parameters (e.g., cell types, model systems, and endpoints) and mechanisms of action shown to be involved in key toxicities that have the potential for assessment via IVIVE. Also, as experts in their field, the speakers will provide knowledge regarding organ system pathophysiology and offer key insights into in silico, in vitro, and systems biology methodology that are essential for successful development of IVIVE platforms. Together, latest developments on assay guidance and strategic IVIVE development can inform participants on best approaches within the field and help address key challenges and gaps faced by investigators. Along with insights into regulatory considerations and future IVIVE perspectives, this course offers key strategies for development, implementation, and advancement of IVIVE practices across research sectors.

IVIVE CE Course Overview. Samantha Faber, Takeda Development Center Americas Inc., San Diego, CA.

Evaluation of Inhalation Toxicity IVIVE and Potential Health Impacts of Tobacco-Free Products and Mixtures. Jingjie Zhang, Altria Client Services LLC, Richmond, VA.

IVIVE Approaches to Drug-Induced Liver Injury: Translating Clinical Findings into Knowledge for Drug Safety Evaluation. Zhichao Liu, US FDA/NCTR, Jefferson, AR.

Developing a DNT Battery for Organophosphorus Flame Retardant-Induced Toxicity for Human Health Risk Assessment. Helena Hogberg-Durdock, NIEHS, Research Triangle Park, NC.

Human 3D Cardiac Microtissues Enable Chamber-Specific Arrhythmic Risk Assessment for Improved Human Safety Standards. Kareen Coulombe, Brown University, Providence, RI.

Strategies and Guidance for Implementation of IVIVE in Chemical Risk Assessment. Jean-Lou Dorne, European Food Safety Authority, Parma, Italy.

Sunday, 1:15 PM to 5:00 PM

PM11

Inhalation Drug Development: Back to Basics

This course will be a take-home course for those new to the inhalation toxicology field and provide regulatory guidance to those not so new to inhalation toxicology.

Chair(s):
Simon Moore, Labcorp Drug Development; and Melanie Doyle-Eisele, Lovelace Biomedical.
Primary Endorser:
Inhalation and Respiratory Specialty Section

Inhalation toxicology has always had an air of mysticism when compared to other routes of administration. This CE course will provide the information to allow better understanding of this perceived dark art. This course will be a take-home course for those new to the inhalation toxicology field and provide regulatory guidance to those not so new to inhalation toxicology. The course will consist of practical aspects of animal studies when it comes to the determination of dose and formulation aspects. Further, this course will provide examples and interpretations on what is adverse and not adverse in reference to histopathological findings in the respiratory tract.

Aerosol Generation Systems and Aerosol Characterization Methodology. Jacob McDonald, Lovelace Biomedical and University of New Mexico, Albuquerque, NM.

Optimization of Dosing Methodology for Animals. Simon Moore, Labcorp Drug Development, Huntingdoneshire, United Kingdom.

Inhalation Dose and Respiratory Physiology. Jeffrey Tepper, Tepper Nonclinical Consulting, San Carlos, CA.

Study Design for Respiratory Toxicology (Drug Development Focus). Matthew Reed, Coelus and University of New Mexico, Albuquerque, NM.

Respiratory Pathology—Differences between Inhalation and Non-inhalation Routes. Nicholas Macri, Labcorp Drug Development, Albuquerque, NM.

Roundtable Discussion—Lessons Learned with Inhalation Drug Development. Melanie Doyle-Eisele, Lovelace Biomedical, Albuquerque, NM.

Sunday, 1:15 PM to 5:00 PM

PM12

Making the Most of Your Data: How to Build Machine-Learning Models for Toxicology

The aim of this course is to provide the participants with a broad understanding of the many benefits of computational toxicology methods, as well as an understanding of the limitations and appropriate use of such methods for successful application depending on the use case.

Chair(s):
Catrin Hasselgren, Genentech Inc.; and Nigel Greene, AstraZeneca.
Primary Endorser:
Computational Toxicology Specialty Section
Other Endorser(s):
Biological Modeling Specialty Section; Drug Discovery Toxicology Specialty Section

Computational toxicology encompasses the development of machine-learning (ML) and mechanistic models and tools applied to datasets of toxicological concern. Applications of such tools span a wide field, encompassing hazard identification, prioritization for experimental testing, optimization of chemical space and chemical risk assessment. These methods are used in many different industry sectors such as consumer products, pharmaceuticals, cosmetics, and agrochemicals, and are widely used in the environmental sector and in governmental or regulatory organizations. The methods employed vary from simple to complex, depending on availability and quality of data, and range from the application of structural alerts to ML models of large-scale biological data and complex systems toxicology modeling. With increased pressure to reduce the number of animal experiments, accelerate the product development cycles and lower costs, computational toxicology is a continuously developing area with yet untapped potential. This course will give a short introduction to the field of computational toxicology, followed by a series of lectures on methods used in building computational models. The first presentation will focus on the data available for model building and how we normalize, clean and prepare the experimental data for model building. The second presentation will describe the different algorithms that could be used and how to select appropriate methods given the data at hand and considerations for how to split data into training versus test sets. The third presentation will focus on how to appropriately evaluate models so as to understand their utility and application in decision-making. The course will end with an interactive exercise where the audience will be asked to vote on the various steps throughout the model building process to reinforce the theory presented in the previous three talks. We will jointly evaluate model performance and utility and lessons learned along the way. The aim of this course is to provide the participants with a broad understanding of the many benefits of computational toxicology methods, as well as an understanding of the limitations and appropriate use of such methods for successful application depending on the use case. The learnings from this course are relevant for attendees from all academic, industry, and government sectors that are looking to explore or expand the use of computational models within their organizations.

Computational Toxicology—Introduction. Catrin Hasselgren, Genentech Inc., South San Francisco, CA.

The Importance of Biological Data Evaluation and Preparation. Fjodor Melnikov, Genentech Inc., South San Francisco, CA.

Method Selection and Best Practices in Model Building. Alexander Tropsha, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Approaches for Effective Model Validation and Testing. Timothy Allen, Ladder Therapeutics, Vancouver, BC, Canada.

Case Study—Let’s Build Models Together! Nigel Greene, AstraZeneca, Waltham, MA.

Sunday, 1:15 PM to 5:00 PM

PM13

Put Your Science Where Your Mouth Is: Practice Makes Progress in Effective Science Communication

Full course information coming soon

Chair(s):
Name, Aff; and Name, Aff.
Primary Endorser:
? Specialty Section
Other Endorser(s):
?; ?

Content here.

Enabling Animal-Free Safety Assessment of Cosmetics Globally. Catherine Willett, Humane Society International, Washington, DC.

Registration Fees for Courses

AM and PM Courses

BY January 27

Early-Bird

  • $150: SOT Member/Global Partner
  • $110: Retired/Emeritus Member
  • $300: Nonmember
  • $90: Postdoc Member/Nonmember
  • $45: Student Member/Nonmember
January 28–February 24

Standard

  • $185: SOT Member/Global Partner
  • $145: Retired/Emeritus Member
  • $335: Nonmember
  • $125: Postdoc Member/Nonmember
  • $80: Student Member/Nonmember
AFTER February 24

Final

  • $220: SOT Member/Global Partner
  • $180: Retired/Emeritus Member
  • $370: Nonmember
  • $160: Postdoc Member/Nonmember
  • $115: Student Member/Nonmember

Sunrise Course (includes breakfast)

Early-Bird
(By Jan. 27)

Standard
(Jan. 28 to Feb. 24)

Final
(After Feb. 24)

SOT Member/Global Partner

$55

$90

$125

SOT Retired/Emeritus Member

$55

$90

$125

Nonmember

$75

$110

$145

Postdoctoral
(SOT Member/Nonmember)

$55

$90

$125

Student
(SOT Member/Nonmember/Undergraduate)

$25

$60

$95

Early-Bird
(By Jan. 27)

SOT Member/
Global Partner

$55

SOT Retired/
Emeritus Member

$55

Nonmember

$75

Postdoctoral
(SOT Member/Nonmember)

$55

Student
(SOT Member/Nonmember/
Undergraduate)

$25


Standard
(Jan. 28 to Feb. 24)

SOT Member/
Global Partner

$90

SOT Retired/
Emeritus Member

$90

Nonmember

$110

Postdoctoral
(SOT Member/Nonmember)

$90

Student
(SOT Member/Nonmember/
Undergraduate)

$60


Final
(After Feb. 24)

SOT Member/
Global Partner

$125

SOT Retired/
Emeritus Member

$125

Nonmember

$145

Postdoctoral
(SOT Member/Nonmember)

$125

Student
(SOT Member/Nonmember/
Undergraduate)

$95