The Continuing Education (CE) Program offers a wide range of courses that cover established knowledge and new developments in toxicology and related disciplines.
Proof of COVID-19 vaccination is required to attend the meeting on-site in San Diego. CE courses will not be livestreamed for remote participation. Many of the CE courses will be recorded and made available for a fee as part of the CEd-Tox: Online Continuing Education Program after the meeting.
Registration for the Annual Meeting and a ticket for the CE course are required to attend.
There has been significant progress globally over recent years in advancing the science to underpin nonanimal cosmetic safety assessment.
There has been significant progress globally over recent years in advancing the science to underpin nonanimal cosmetic safety assessment. In addition, citizen-led initiatives that prohibit animal testing of cosmetics and cosmetic ingredients are expanding geographically every year. These advances are leading to the need for global capacity building among the regulated and regulatory communities for completely animal-free safety assessment of consumer products. In the European Union, there has been a ban on animal testing of cosmetics since 2004 and a sales ban on cosmetics tested on animals since 2013; nevertheless, because of testing requirements in other sectors or geographies, animal testing of cosmetics continues. To enable confident decision-making regarding the safety of cosmetics and personal care products, it is important to build confidence in the requisite methodologies based on experience. Toward this aim, an in-depth educational program has been developed by the Animal-Free Safety Assessment (AFSA) Collaboration, a partnership of nonprofit organizations and industry. Achieving a confident risk assessment of a consumer product or ingredient without data from new animal testing requires a novel approach to the assessment, as well as integration of several types of in silico and in vitro data. This Continuing Education course will provide a primer on the necessary tools, including understanding the regulatory playing field, risk assessment problem formulation, estimating consumer exposure, in silico and in vitro approaches to filling data gaps, and estimating an in vitro point of departure—plus, a case example demonstrating how to combine all these elements into a well-documented assessment based on the modules developed by the AFSA Collaboration. Each of the presentations, given by a partner representative with the relevant expertise, will include a set of learning objectives to stimulate audience participation; after the presentations and before the open discussion, there will be a short crowdsourced quiz via Slido on the material presented. An open discussion/roundtable will include one to two participants with regulatory experience.
Enabling Animal-Free Safety Assessment of Cosmetics Globally. Catherine Willett, Humane Society International, Washington, DC.
The Global Cosmetics Regulatory Landscape. Jay Ingram, Delphic HSE, Surrey, United Kingdom.
Problem Formulation: Setting the Stage for the Risk Assessment Length. Shashi Donthamsetty, International Flavors & Fragrances Inc., New York, NY.
Estimating Consumer Exposure. Christina Hickey, Firmenich SA, New York, NY.
Internal Exposure. Rebecca Clewell, 21st Century Tox Consulting, Durham, NC.
In Silico and In Vitro Data Generation: Strategies for Addressing Data Gaps to Inform an NGRA. Hans Raabe, Institute for In Vitro Sciences Inc., Gaithersburg, MD.
Integration of New Approach Methodologies for Cosmetic Safety Decision-Making. Matt Dent, Unilever Safety and Environmental Assurance Centre, Bedfordshire, United Kingdom.
Panel Discussion with Additional Regulatory Perspectives. Tala Henry, US EPA; and Eric Vaillancourt, Health Canada, Ottawa, ON, Canada.
Over the last several decades, a great deal of progress has been made in the development of alternative methods to assess immunotoxicity, for both inappropriate immunostimulation and immunosuppression.
Over the last several decades, a great deal of progress has been made in the development of alternative methods to assess immunotoxicity, for both inappropriate immunostimulation and immunosuppression. Immunotoxicology hazard identification requires novel approaches and strategies, possibly without the use of animals to be in line with the vision of toxicology in the 21st century. In vitro methods anchored to adverse outcome pathways (AOPs) currently under development or already accepted at the Organisation for Economic Co-operation and Development (OECD) level, associated with identified key characteristics (KCs) of immunotoxicants, and the combination of complementary information, in the context of an Integrated Approaches to Testing and Assessment or a Defined Approach, offer the opportunity to identify the hazard that xenobiotics may pose to the immune system. This Continuing Education course aims to highlight animal-free approaches in immunotoxicology, and participants will learn how to apply these novel strategies to gain an understanding of how and if substances modulate immune processes. The course will present the KCs of immunotoxicants as an approach for hazard identification and will provide examples demonstrating the use of this framework in the characterization of the toxicity of immunotoxic agents. The use of KCs for the design of tests to evaluate the hazards of novel chemicals to complement or replace existing approaches will be emphasized. In the second presentation, the defined approaches for skin sensitization recently adopted at the OECD level will be presented. Defined approaches have been demonstrated to be more reliable and human relevant than stand-alone in vitro tests or the commonly employed in vivo test methods. The third presentation will discuss integrated testing strategies for the identification of xenobiotic-inducing immunosuppression, including high-dimensional profiling pathway analyses and computational approaches to integrating immune-related data and outcomes assessments. Finally, the Universal Immune System Simulator (UISS), a simulation framework to model the immune system, will be introduced. The UISS software is free and has been used for hazard characterization of pharmaceuticals. The application of this software for evaluating environmental contaminants will be demonstrated. The presentation of these novel approaches will enable course participants to gain an understanding of how mechanistic-based testing strategies can be applied to evaluate the adverse effects of chemicals on immunity.
Key Characteristics of Immunotoxicants: The Way Forward? Dori R. Germolec, NIEHS, Morrisville, NC.
OECD and Defined Approaches to Identify Contact Allergy: From Hazard to Quantitative Risk Assessment. Nicole Kleinstreuer, NIEHS, Morrisville, NC.
Integrated Testing Strategy for Immunosuppression. Mark Collinge, Pfizer Inc., Groton, CT.
The Universal Immune System Simulator: An In Silico Model to Predict the Risk Associated with Exposure to Immunotoxicants. Francesco Pappalardo, Università di Catania, Catania, Italy.
Besides traditional, narrative reviews, other review types are increasingly being used in toxicology and recognized for their strengths.
Besides traditional, narrative reviews, other review types are increasingly being used in toxicology and recognized for their strengths. For instance, systematic review has joined the narrative review on the short list in the hasten publication type filter on PubMed. Systematic reviews, a format originating from the clinical research field, offer balanced answers to predefined questions with transparent steps and comprehensive consideration of diverse, including conflicting, results. They are considered the gold standard in many agencies for hazard identification and/or risk assessment of carcinogenic and noncarcinogenic effects from chemical, physical, and biological agents, mixtures, lifestyles, and other scenarios. Evidence map (survey the available research evidence), scoping review (evidence map with a descriptive narrative summary of the results, typically without data extraction or study quality assessment), rapid systematic review (faster completion than a systematic review with or without review shortcuts), umbrella review, and mixed type of review each can fit different needs while requiring fewer resources than a systematic review. This course is designed for toxicologists at all stages of their careers and will explain the review types, how to know which type is right for your question and situation, how to complete selected types of the review, and how to publish them, including interim products, in peer-reviewed journals. Many early steps in the process are highly similar among these highlighted review types, and participants will be able to build knowledge and know-how by following the presentations in the designed order. At the end of the course, the participants will be able to (1) distinguish different types of reviews; (2) prepare an evidence map, scoping review, rapid systematic review, or systematic review that fits their needs; (3) use computational tools to simplify and fasten the process; and (4) write a competitive manuscript to amplify the impact of their work.
Review Types in Toxicology. Amy Wang, NIEHS/NTP, Research Triangle Park, NC.
Fit for Purpose: Scoping Reviews and Systematic Evidence Mapping to Support Decision-Making. Vickie R. Walker, NIEHS/NTP, Research Triangle Park, NC; and Andrew Rooney, NIEHS/NTP, Research Triangle Park, NC.
How to Conduct Systematic Reviews and Rapid Systematic Reviews. Xabier Arzuaga, US EPA, Washington, DC.
Tools to Help Your Review. Ruchir Shah, Sciome LLC, Durham, NC.
Success in Publishing Evidence Reviews: An Editor’s Strategy. Paul Whaley, Lancaster University, Lancaster, United Kingdom.
The fields of exposure science and toxicology are changing, and these changes have the potential to improve our ability to assess risks from concurrent exposures to multiple chemicals.
The fields of exposure science and toxicology are changing, and these changes have the potential to improve our ability to assess risks from concurrent exposures to multiple chemicals. The changes include advances in exposure monitoring; the development of structure-based predictions of chemical properties relevant to exposure assessment and/or relevant PK modeling of internal doses; the development of new approach methodologies (NAMs); advances in modeling variation and uncertainty in exposure and dose-response; and the creation of curated databases of information on toxicity and exposure. This course presents a review of how these advances can, and likely will, change mixture risk assessments. The course will begin with an overview of the existing approaches for mixture risk assessment, the limitations of these approaches, and the identification of the types of information and tools needed to improve the assessments. The remainder of the course will consist of four talks on how changes in scientific disciplines relevant to mixture toxicology, such as cumulative exposure assessment, toxicokintics, toxicodynamics, and data organization, are helping to address the needs of mixture risk assessors. Each of the talks will describe how advances in the field are improving the ability to assess mixture risks (with case studies) and what could be done in the future. The first talk will focus on how advances in exposure science can be used to improve our ability to rapidly characterize multiple chemical exposures in an individual and how these combined exposures vary across individuals. The second talk will address advances in our understanding and ability to model chemical interactions that involve the toxicokinetics of the chemicals. The third talk will discuss the testing of mixtures of chemicals using in vitro assays to characterize interactions of chemicals in terms of common molecular initiating events, key events, and certain apical effects. The final talk will recast our understanding of the mixture risk assessment process using the concepts of the aggregate exposure pathways (AEP), adverse outcome pathways (AOP), and AEP–AOP networks. This talk will include a description of a proposed taxonomy for chemical interactions that can help organize existing data on mixture toxicity. Together, the talks will describe the relevance of scientific advances to the assessment of risks from exposures to multiple chemicals. The course will discuss assessing risks from exposure to discrete mixtures of chemicals and from exposures to multiple sources (cumulative exposures). While many of the issues discussed apply to ecological effects of mixtures, this course will focus on the effects on human health.
Introduction and Overview of the Key Elements of Mixture Risk Assessment. Richard Hertzberg, Emory University, Atlanta, GA; and Allison Phillips, US EPA, Research Triangle Park, NC.
Advances in Exposure Science and the Improved Characterization of Combined Exposures. Kristin Isaacs, US EPA, Research Triangle Park, NC.
Advances in Pharmacokinetics and Their Implications for Mixture Risk Assessment. Sami Haddad, Université de Montréal, Montreal, QC, Canada.
Surveying the Use of New Approach Methodologies in Component-Based and Whole Mixture Risk Assessment Contexts. Cynthia Rider, NIEHS/NTP, Research Triangle Park, NC.
Organizing Information on Chemical Interactions Using a Framework Based on Networks of Linked Aggregate Exposure Pathways and Adverse Outcome Pathways (AEP-AOP Networks). Paul Price, Independent Researcher, Cedar Rapids, IA.
Age and reproductive status are often overlooked variables in mammalian nonclinical studies, but they can have a significant impact on the evaluation of the reproductive system, the interpretation of potential experimental- or test article–related findings, and ultimately the risk assessment.
Age and reproductive status are often overlooked variables in mammalian nonclinical studies, but they can have a significant impact on the evaluation of the reproductive system, the interpretation of potential experimental- or test article–related findings, and ultimately the risk assessment. The reproductive system of male and female test species undergoes considerable changes as it transitions from immature to puberty and into fully sexually mature. The timing of puberty and sexual maturation varies across species and sexes and is a major variable in acute/subchronic and reproductive toxicity testing. In females, there also is an age-associated decline in reproductive performance, termed reproductive senescence. In chronic toxicity testing, the effects of reproductive aging are not likely to be seen in nonrodents (e.g., dogs, nonhuman primates, and minipigs) because of their relatively long life spans; however, this can be a major complicating factor for female rodents. An appreciation and understanding of these developmental and age-related changes in the reproductive system is critical to study design, execution, and interpretation for a variety of in vivo experimental disciplines, including toxicology (general, juvenile, investigative, DART, etc.), mouse models, and discovery efforts. The objectives for this course are to provide attendees with an overview of the basic biology of sexual maturation in males and females and reproductive aging in females and to review the effects on study design, data interpretation, and extrapolation to humans.
This course will complement the Continuinig Education (CE) course “The Male Reproductive Tract: Development, Toxicology, and Pathology,” which was presented as part of the scientific program during the Virtual 2020 SOT Annual Meeting, and the CE course “Development, Toxicology, and Pathology of the Female Reproductive Tract: Interpretation of Findings from the Pathologist and Regulatory Perspectives,” which was presented as part of the scientific program during the Virtual 2021 SOT Annual Meeting. These courses are available as part of SOT CEd-Tox, the Society’s online Continuing Education course program.
Introduction. Christopher J. Bowman, Pfizer Inc., Groton, CT.
Sexual Maturation in the Male and Female Rodent. Wendy Halpern, Genentech Inc., South San Francisco, CA.
Sexual Maturation in Large Animal Species. Justin Vidal, Charles River, Mattawan, MI.
Reproductive Senescence in the Female Rodent. Tammy Stoker, US EPA, Research Triangle Park, NC.
The Art of Senescence—Study Design and Data Interpretation. Pragati S. Coder, Charles River Laboratories Ashland LLC, Ashland, OH.
Drug discovery toxicology starts at the very beginning, when a new target is proposed for entry into the portfolio.
Drug discovery toxicology starts at the very beginning, when a new target is proposed for entry into the portfolio. After confirmation of the target, the discovery toxicologist will serve as an integral member in lead optimization and candidate selection for progression into GLP toxicology studies. A lead candidate is selected through rigorous in silico and in vitro screening and subsequent in vivo pilot toxicology studies that enable a preliminary assessment of safety. In this course, the speakers will provide a comprehensive overview of the target toxicity evaluation, chemical series and compound de-risking strategies, and approaches leading to lead identification and the first in vivo pilot toxicology studies. The identification of any potential liabilities associated with the target and their relevance for the patient population and indication contributes to the decision to invest in the exploration of a particular target. After the decision is made to drug a chosen target, the discovery toxicologist will become a critical member of the early discovery team, where the selection of lead compounds will be discussed to finally enable the identification of a candidate to take into GLP toxicology studies. To select a molecule with a safety profile that provides an optimal chance of clinical success, strategies are developed by selecting a panel of in silico, in vitro, and in vivo experiments. How these in silico and in vitro strategies are developed to provide optimal chemical series and compound de-risking will be discussed. Other presentations will focus on the in vivo experiments where PK/PD modeling and ideally early human dose predictions are needed to drive decisions on dosing frequency and dose selection. Early in vivo pilot toxicology studies will be discussed, with a focus on their design, interpretation, and impact. The course will conclude with an interactive investigative toxicology case study session where different case studies will be discussed with the audience. While this session focuses on strategies for small molecules, the overall concepts, approaches, and technologies are generally informative for biotherapeutics and new chemical modalities.
Target Safety Assessments: Knowledge Is Power. Ruth Roberts, ApconiX, Cheshire, United Kingdom.
Chemical Series and Compound De-risking: What Do We Focus On and Why? Nigel Greene, AstraZeneca, Waltham, MA.
Pharmacokinetics as an Integral Part of Early Drug Development. Sabrinia Crouch, Neurocrine Biosciences Inc., San Diego, CA.
Early In Vivo Pilot Toxicology Studies in Drug Discovery: Study Designs, Strategies, and Objectives. Jonathan Maher, Theravance Biopharma, South San Francisco, CA.
Discovery Toxicology Case Studies: An Interactive Session. Nardos Tassew, Genentech Inc., South San Francisco, CA; and Qin Wang, Takeda Pharmaceutical Company Limited, San Diego, CA.
Hearing loss is a major global health issue affecting 1.5 billion people worldwide.
Hearing loss is a major global health issue affecting 1.5 billion people worldwide. Prevalence is increasing dramatically: in 2050, one in four people will have some hearing impairment. Acquired hearing loss is attributed to different environmental factors, including aging, noise exposure, and intake of ototoxic medicines. Ototoxicity resulting in inner ear damage is a leading cause of acquired hearing loss worldwide. About a billion people are at risk of avoidable hearing loss, according to the World Health Organization (WHO). This could be minimized or avoided by early testing of hearing functions in the preclinical phase. While the assessment of ototoxicity is well defined for drug candidates in the hearing field (i.e., required testing for drugs that are administered by the otic route and expected to reach the middle or inner ear during clinical use), ototoxicity testing is not required for the other therapeutic areas. Unfortunately, this has resulted in more than 200 ototoxic marketed medications. This course will provide an interactive learning opportunity to understand the key considerations for determining a drug candidate’s ototoxicity. Discussions will focus on four aspects of ototoxicity: (1) the burden of ototoxicity, the physiopathology of hearing loss, and current therapeutic strategies to treat deafness; (2) why, when, and how to perform preclinical ototoxicity studies; (3) regulatory perspectives; and (4) ototoxicity case studies. The target audience includes toxicologists involved in the development of potentially ototoxic drugs, pharmaceutical companies looking to develop or repurpose drugs for hearing disorders, and those seeking scientific and operational expertise to make sure that drug candidates do not affect auditory mechanisms.
The Global Burden of Ototoxicity: Epidemiology, Physiopathology, and Therapeutic Strategies. Marie-Pierre Pasdelou, CILcare, Lexington, MA.
Nonclinical Ototoxicity Testing Overview and Histopathologic Assessment in Nonclinical Studies. Marie-Pierre Pasdelou, CILcare, Lexington, MA.
Hearing Loss, Ototoxicity, and the Importance of Adequate Testing in Nonclinical Safety Studies: A Regulatory Perspective. Christopher Toscano, US FDA/CDER, Silver Spring, MD.
Evaluating Ototoxic Effects of Medical Devices for Tympanic Membrane Repair. Elaine Horn-Ranney, Tympanogen, Richmond, VA.
How to Select the Best Candidate with Minimal Ototoxicity. Sven Hobbie, Universität Zürich, Zurich, Switzerland.
This course will focus on the principles of nonclinical pediatric safety assessments.
This course will focus on the principles of nonclinical pediatric safety assessments. For pharmaceuticals, the ICH S11 Guideline on Nonclinical Safety Testing in Support of Development of Paediatric Pharmaceuticals was recently finalized and outlines a weight of evidence approach to deciding whether a juvenile animal study is warranted. Once it is decided a juvenile animal study is needed, there are many decisions that need to made, as there is no set default study design. The objectives for this course are to provide attendees with an overview of the regulatory rationale to conduct juvenile toxicology studies, the comparative biology of organ systems that develop postnatally, practical study design considerations, and case studies exemplifying data interpretation and risk assessment.
Overview of Juvenile Toxicology. Jia Yao, US FDA/CDER, Washington, DC.
Postnatal Organ System Development across Species. Wendy Halpern, Genentech Inc., South San Francisco, CA.
Designing Juvenile Animal Studies. Susan Laffan, GlaxoSmithKline, Collegeville, PA.
Juvenile Animal Studies: Case Studies and Risk Assessments. Katie Turner, Janssen Research & Development, Spring House, PA.
The human microbiome describes the collective genomes, and encoded functions, of the trillions of bacterial cells that live on and in the human body.
The human microbiome describes the collective genomes, and encoded functions, of the trillions of bacterial cells that live on and in the human body. Host-associated microbiomes produce metabolites that impact human host cells in myriad ways, including interaction with host metabolic and immune signaling. The microbiome’s relationship to human health is made more complex when considering its interactions with the environment and the chemicals within. In fact, the role of the microbiome in modulating chemical exposure and the role exposure plays in shaping the microbiome are becoming more critical considerations for mechanistic toxicity studies and chemical evaluations. Recent technological advances that provide a deeper understanding of the microbial milieu are outpacing the incorporation of microbiome analyses in the field of toxicology. The objective of this course is to provide attendees with an overview of reliable and robust approaches for analyzing the microbiome’s composition, function, and role as a potential mediator of toxicity. Speakers with expertise in microbiome analysis in the context of exposures will present (1) an overview of the importance of considering the microbiome in the context of toxicology studies; (2) an explanation of cutting-edge technologies currently used to assess changes in microbiome composition and function and their applications to toxicology; (3) examples of the use of in vitro and alternative models for the microbiome and toxicity; (4) guidelines for the use of rodent models in assessing the microbiome as a mechanism of action for toxicity of chemicals; and (5) a summary of current translational approaches for studying the microbiome. Participants will gain an understanding of the utility of available models and methodologies for studying the microbiome, xenobiotic exposure, and human health and toxicity.
Why Consider the Microbiome in the Context of Exposures and Toxicity? Anika Dzierlenga, NIEHS, Durham, NC.
Methods and Approaches to Evaluate the Microbiome. Rob Knight, University of California San Diego, San Diego, CA.
In Vitro and Alternative Models for the Assessment of Chemical-Microbiome Interactions. Tamara Tal, Helmholtz Centre for Environmental Research, Leipzig, Germany.
Rodent Studies to Evaluate the Microbiome as a Mechanism of Toxicity. Sangeeta Khare, US FDA/NCTR, Jefferson, AR.
Translational Approaches for Toxicology, the Microbiome, and Human Health. Yvonne Huang, University of Michigan, Ann Arbor, MI.
The vascular network has long been known as a target of toxicity following exposure and absorption.
The vascular network has long been known as a target of toxicity following exposure and absorption. Furthermore, overall health and well-being of the cardiovascular system is highly dependent on a functional vascular network that can respond dynamically to ever-changing physiological demands. However, the difficulty of measuring functional and structural changes in the vascular network can limit toxicological findings. This course will specifically deal with methodology related to quantitating vascular toxicity at the cellular, tissue, and whole-network levels. This course’s presentations will describe techniques to elucidate functional vascular outcomes, from cellular to system-wide. After a brief introduction on advanced physiology of the vascular system, including structure, function, fluid dynamics, and pathology, the course will focus on isolated vascular and cellular techniques in rodent models to determine changes in vascular reactivity, vasomotor responses, and barrier integrity in isolated tissue and cells, as well as reactivity of these models to absorbed serum toxicants, followed by a specific discussion of the endothelial cell and vascular remodeling in the cerebrovascular network. Intravital microscopy as a mechanism for functional assessment of intact tissues in a diverse set of vascular beds will be discussed, as will the utilization of ultrasonography to determine in vivo uterine artery blood flow during gestation. In addition, the methodology aspects of endothelial cell function noninvasely, as well as cell harvesting from human volunteers, will be outlined. This course will be of interest to a broad scope of scientists that are increasingly being asked to consider the effects of novel compounds and toxicants on the physiology of the vascular network. Furthermore, this course builds on a 2013 Continuing Education course and a 2019 Platform Session.
Endothelial Cell Role in Mediating Toxicity, Inflammation, and Pathology: Implications for Study Design. Matthew Campen, University of New Mexico, Albuquerque, NM.
Assessing Toxicity in the Cerebral Microvasculature. Amie Lund, University of North Texas, Denton, TX.
Methodological Principles of Microvascular Toxicology. Timothy Nurkiewicz, West Virginia University, Morgantown, WV.
The Role of Uterine Arterial Remodeling in Fetal Development and Adverse Pregnancy Outcomes. Colette Miller, US EPA, Research Triangle Park, NC.
Evaluating Endothelial Cell Function—From Bedside to Bench. Jessica Fettermann, Boston University, Boston, MA.
Neurotoxicological effects following chemical exposure range in structural and functional alterations within the anatomically complex brain.
Neurotoxicological effects following chemical exposure range in structural and functional alterations within the anatomically complex brain. Traditional histological or ’omic techniques used to identify potential toxicity have limitations in specificity or a comprehensive understanding of altered connectivity of the 100 billion interconnected neurons. The objective of this course is to provide toxicologists with a better understanding of novel neuroscience techniques that provide optimized visualization of spatial alterations and behavioral phenotyping that can be applied to and advance neurotoxicology studies. This course is designed to highlight and educate all levels of scientist on the current approaches in neuroscience research that can be used in the field of toxicology to evaluate the context of brain morphogenesis and the significance of toxicant-induced disruption and will demonstrate how the 3D in vitro system can model the complex multicellular brain environment found in vivo. Different approaches to examining intact brain tissue capturing neurocircuit morphology will be discussed, including (1) a novel method to clear the tissue, enabling the visualization and spatial rotation of the regions (or systems) of interest from animals; (2) fMRI methods to provide highly detailed models of neurocircuitry to gain new insights into exposure effects; and (3) proficient behavioral phenotyping models and in vivo neurocircuit visualization to identify neurotoxic chemicals. Many times, the neurochemical effects are unknown and have no targeted system. The course also will discuss spatial profiling on slide-mounted tissue and the capability of choosing a neuronal region of interest to perform genomic profiling; this can distinguish the chemical effects at a genomic level within specific regions of the brain. Providing participants with a comprehensive understanding of the new techniques and their application in neurotoxicology using real-world examples, the course will allow the audience to interact with experts who are currently using the techniques and to ask questions for future application to their own research. While the course focuses on neurotoxicology, these techniques are easily transferred to different areas of research, including neurodegeneration and drug discovery, as well as other organ systems. The five-minute introduction will lay out the agenda of the course, including the overall goals, speaker lineup, and intended outcome. All five speakers will have a total of 30 minutes each, which includes time for questions following each talk. There will be a 10-minute panel discusssion followed by a 10-mininute break after speaker 2. There also will be an additional 20 minutes of panel discussion after the last speaker, providing ample opportunity for participation and Q&A.
Microphysiological Systems of the CNS to Bridge between In Vivo and In Vitro. Helena Hogberg, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
Exploring 3D Structures and Biomarker Distributions in Intact Transparent Brain and Potential Applications in Neurotoxicology. Sharla White, Clear Light Biotechnologies Inc., San Francisco, CA.
Combined Magnetic Resonance Histology and Light Sheet Whole-Brain Imaging. G. Allan Johnson, Duke University Center for In Vivo Microscopy, Durham, NC.
Overview of Novel Approaches for Neurotoxicological Behavioral Assessment and Neurocircuit Visualization. Jesse Cushman, NIEHS, Durham, NC.
Utilization of Spatial Transcriptomics and Proteomics Analysis of Targeted Neuronal Tissue Microenvironments. Colleen Urben, NanoString, Madison, WI.
Although read-across approaches have been used for many years to fill data gaps for chemicals lacking experimental toxicology data, recent advances in computational toxicology and the development of new approach methodologies (NAMs) have extended these approaches to allow for better mechanistic understanding.
Although read-across approaches have been used for many years to fill data gaps for chemicals lacking experimental toxicology data, recent advances in computational toxicology and the development of new approach methodologies (NAMs) have extended these approaches to allow for better mechanistic understanding. The initial foundation for read-across was based on similarity in chemical structure and physicochemical properties; however, recent approaches also include consideration of toxicokinetic similarity and common toxicologic mode of action. This course will provide important background on read-across principles and will describe the latest computational tools that may assist with toxicological read-across. The importance of applying expert judgment to interpret the output from computational tools will be discussed. Case studies will present a variety of perspectives on current applications of read-across to human health risk assessment (i.e., US and international regulatory agencies, NGOs, industry, and consultants). The course is outlined as follows: The first talk will provide an introduction, focusing on common principles and techniques employed in read-across, regulatory frameworks, and available guidance for best practices. The second talk will then describe available tools used for different aspects of selecting and evaluating analogues in support of a toxicological read-across strategy. The third talk will describe application of the European Chemicals Agency (ECHA) Read-Across Assessment Framework (RAAF) to predict subchronic and developmental health effects for a target chemical. The fourth presentation will expand on the Presentation #3 case study to describe how broadening the use of read-across can help fill multiple data gaps to support selection of safer chemical ingredients. Finally, the fifth talk will discuss the historical and future directions of read-across under Canada’s Chemicals Management Plan, including case studies that utilize NAM data. Read-across methods have evolved rapidly during the past several years. This Continuing Education course will provide a thorough overview of existing methods with a view toward the future of incorporating mechanistic NAM data to support read-across approaches. Thus, this course will offer broad appeal to audience members of different backgrounds and may be of interest to trainees interested in a career in regulatory toxicology or risk assessment.
Introduction to Read-Across: Principles, Techniques, and Frameworks. Lucina Lizarraga, US EPA/CPHEA, Cincinnati, OH.
Tools to Assist in Toxicological Read-Across. Mary Kawa, SRC Inc., Syracuse, NY.
Application of the ECHA Read-Across Assessment Framework (RAAF) to Predict Subchronic and Developmental Health Effects of Trometamol. Pam Spencer, ANGUS Chemical Company, Buffalo Grove, IL.
Broadening the Use of Read-Across to Guide the Selection of Safer Chemical Ingredients. Chris Bartlett, ChemFORWARD, Spokane, WA.
Historical and Future Directions of Read-Across under Canada’s Chemicals Management Plan: From Structural Similarity to Advances in Incorporating New Approach Methodologies to Support Substance Groupings. Matthew Gagne, Safe Environments Directorate, Ottawa, ON, Canada.