SOT Component Groups (Regional Chapters, Special Interest Groups, and Specialty Sections) and Committees host webinars throughout the year. Webinars are an effective distance-learning method intended to impart scientific knowledge to members of each group as well as the SOT membership at large. These webinars are just one of the many benefits of SOT membership.
Upcoming webinars for January and February 2020 are listed here.
Rapid Hazard Identification of Environmental Chemicals and Mixtures
Date and Time: Wednesday, January 8, 2020, 3:00 PM–4:30 PM (ET)
Host: Risk Assessment Specialty Section (RASS), co-sponsored with the Mixtures Specialty Section (MSS)
Registration is not required.
Speaker:
Ivan Rusyn, MD, PhD
Department of Veterinary Integrative Biosciences
College of Veterinary Medicine & Biomedical Sciences
Texas A&M University
Assessment of health effects of environmental mixtures still relies on knowledge of individual chemicals and limited animal and epidemiological studies. The traditional debate regarding the health hazard of mixtures is centered on the choice between the “additivity of dose,” or “additivity of the adverse effect.” The most recent focus in research on mixtures is on improvements in analytical techniques and exposomics, deciphering exposure-wide associations from biomonitoring data and health outcomes, and improving epidemiological methods to dissociate potential interactions among agents in a population. There has been less progress in harnessing the power of high-throughput in vitro screening to rapidly evaluate a large number of chemical combinations to identify cumulative effects or to screen real-life environmental samples. A combination of in vitro human population-based cytotoxicity screening followed by dosimetric adjustment can inform quantitative evaluation of human health hazards from complex mixtures. This presentation will demonstrate how a multi-cell-type human in vitro model can be used for testing mixtures for rapid hazard identification and grouping with known human health hazards. Examples from disaster response scenarios will be presented to illustrate the approach.
IVAMSS Webinar: 2019 Student Research Award Winners
Date and Time: Thursday, January 9, 2020, 11:00 AM–12:00 Noon (ET)
Host: In Vitro and Alternative Methods Specialty Section
Registration is required.
Speaker: Eva Vitucci
Presentation Title: Piecing Together the Puzzle: Identifying the Role Oxidative Stress and the Alveolar Epithelium Play in Air Pollution Induced Cardiovascular Disease
An estimated 3.5 million people die every year from air pollution–induced cardiovascular disease (API-CVD); however, while in vivo data have demonstrated associations between induced CVD and systemic oxidative stress, the causative molecular mechanisms driving API-CVD are still poorly understood. To identify the mechanisms of action driving API-CVD, we developed a unique, tri-culture in vitro model that represents the interface of the alveolar epithelial barrier (AEB) and the cardiovascular system. We hypothesized that air pollutant exposure of human alveolar-like epithelial cells (H441) would induce oxidative stress in adjacent, but physically separated, human pulmonary vasculature cells, leading to vascular damage. To test this hypothesis, we exposed confluent, electrically resistant, and small molecular-impermeable monolayers of H441 cells, grown on the apical surface of Transwell permeable membranes, to the ubiquitous air pollutant, diesel exhaust particulates (DEP), with human lung fibroblasts on the underside of the Transwell membrane and human microvascular lung endothelial cells (HULEC) in the basal compartment. Upon DEP exposure, we identified a variety of oxidative stress responsive genes induced in the directly exposed H441 cells and in the indirectly exposed HULEC, including heme oxygenase 1 (HMOX-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1). These changes in gene expression occurred despite a lack of change in trans-epithelial electrical resistance (TEER) and small molecule (20kDa fluorescein isothiocyanate (FITC)-dextran) permeability, suggesting that they result from the release of epithelial/fibroblast-derived mediators and/or compounds/metabolites that traverse the epithelial cells. Collectively, these data suggest that induction of oxidative stress in nearby endothelial cells may be mediated by epithelial cells and may be an important mechanism of API-CVD. We conclude that we have developed a relevant in vivo–like in vitro model of the AEB-cardiovascular system interface that can be used to identify the elusive molecular mechanisms driving API-CVD. Ultimately, data derived from this model can be used to identify therapeutic targets, biomarkers of both susceptibility and exposure effects, and can encourage the continued development of similar biomimetic models, resulting in a reduction of nonessential animal testing.
Speaker: Jinpeng Li
Presentation Title: Functional Comparison of HepaRG Cells and Primary Human Hepatocytes in Monolayer and Spheroid Culture as Repeated Exposure Models for Hepatotoxicity
Reliable and effective prediction of hepatotoxicity resulting from repeated exposure to chemicals is of critical importance for the safety assessment of chemicals. However, in vitro long-term repeated-exposure studies are difficult to conduct using conventional hepatocyte monolayer cultures owing to their rapid de-differentiation and subsequent loss of hepatocyte function. Toward this end, significant advancements have been made to maintain hepatic physiology for an extended period of time by culturing hepatocytes in vitro as three-dimensional (3D) spheroidal aggregates. Here, we compared two promising model systems, HepaRG and primary human hepatocytes (PHH), in both 3D spheroid and traditional 2D monolayer cultures to evaluate their potential as predictive models for assessment of hepatotoxicity. When compared with 2D cultures, cells in spheroid culture maintained higher levels of viability for a longer duration. Likewise, functional characterization revealed higher levels of xenobiotic metabolic activity (CYP1A2, CYP2B6, and CYP3A4) and urea production in spheroid versus 2D cultures. In addition, spheroid cultures showed increased sensitivity to a set of hepatotoxic compounds (ibuprofen, ibufenac, acetaminophen, and aflatoxin B1) after repeated exposure (e.g., EC50 of aflatoxin B1 was reduced by 84% in PHH and 68% in HepaRG spheroids as compared with respective 2D cultures), and the sensitivity was further elevated by extended exposure duration (e.g., EC50 of aflatoxin B1 was further reduced by 25% in PHH and 73% in HepaRG spheroids when treated for an additional week). Moreover, HepaRG spheroids exhibited similar sensitivity as PHH spheroids, especially in extended exposure, suggesting that HepaRG could be a reliable surrogate for PHH and serve as a repeated-exposure model to predict hepatotoxicity.
Best of the Dermal Toxicology Specialty Section: 2019 Scientific Award Winners
Date and Time: Monday, January 13, 2020, 1:00 PM–2:00 PM (ET)
Host: Dermal Toxicology Specialty Section (DTSS)
Registration is required.
The DTSS presents annual awards for scientific studies related to toxicity of the skin. In 2019, three recipients were chosen from the members of this section based on their scientific accomplishments. The objective of this webinar is for the recipients to showcase their award-winning research.
Speaker:
Yoke-Chen Chang, PhD
Rutgers, The State University of New Jersey
Awarded the DTSS Annual Paper of the Year Award, this work investigated the expression of cytokines and chemokines in mouse skin treated with the chemical warfare agent sulfur mustard. They found that inflammatory cell-derived mediators contribute to the pathogenesis of sulfur mustard–induced skin damage.
Speaker:
Xue (Lucia) Liu, PhD
NIH
Dr. Liu and her collaborators developed a novel bio-printed vascularized full-thickness skin equivalent and a reconstructed human epidermis in a multi-well plate format. The purpose for the development of these three-dimensional tissue models is high-throughput drug screening. The tissues developed in this study offer an in vitro approach for understanding the pharmacologic and toxicologic mechanism of action of drugs applied to the skin.
Speaker:
Sarah Dickinson
University of Rochester
Recent evidence suggests that sunscreens, used to protect the skin from damaging ultraviolet radiation from the sun, have off-target effects. The results from this study suggest that the sunscreen octinoxate modulates AhR activity via inhibition of cytochrome P450 1A1. Alteration of AhR activity and signaling has many potential implications on the functions of skin.
Microbiome: Missing Piece in the Diet/Health Puzzle
Date and Time: Wednesday, January 15, 2020, 11:00 AM–12:30 PM (ET)
Host: Food Safety Specialty Section (FSSS)
Registration is required.
Appropriate mutualistic and commensal host/microbiome interactions provide beneficial effects to one or both species, while adverse host/microbiome interactions contribute to disease. Two speakers will describe the effects of diet and foodborne agents on gut microbiota and the effects of gut dysbiosis on health.
Speaker:
Tiffany Weir, PhD
Assistant Professor
Department of Food Science and Human Nutrition
Colorado State University
The gut microbiota have emerged as an important regulator of human health. Imbalances in the gut microbiota, referred to as dysbiosis, have been associated with numerous diseases, both within the intestines as well as in peripheral tissues in organs. Gut dysbiosis is often characterized by reduced microbial diversity and loss of functionality and can lead to increased intestinal inflammation and loss of gut barrier function. While numerous factors can impact the intestinal microbiota, including age, stress, medications, pollutants, and exercise, diet has the greatest potential to modify the microbiota. Our laboratory studies how diet-induced alterations to the microbiota can prevent or increase the risk of developing cardiometabolic diseases. In this webinar, we will explore the role the microbiota play in disease development and examine some of the underlying mechanisms and how external factors shape the microbiota, with a focus on dietary components.
Speaker:
Sangeeta Khare, PhD
Research Microbiologist
Division of Microbiology
US FDA/NCTR
This talk will provide approaches for the risk assessment of intentional and unintentional use of antimicrobials (metal-based nanomaterial) and antimicrobial residues (antibiotics). Usually these products are used as health supplements or are present as drug residues in consumer products. Interactions of these products with the gastrointestinal tract might have an adverse effect on the commensal microbiota, impact antimicrobial resistance, and alter the host immune responses and intestinal permeability.
Impact of 2017/745 EU Medical Device Regulation (MDR) on Biological Evaluation of Medical Devices
Date and Time: Thursday, January 16, 2020, 11:00 AM–12:00 Noon (ET)
Host: Medical Device and Combination Product Specialty Section (MDCPSS)
Registration is required.
Speakers:
Jeremy Tinkler
Director of Regulatory Consultancy and Quality Assurance
MedPass International
Rachel Hardy
Senior Strategy Consultant
MedPass International
This webinar will focus on the impact of the 2017/745 EU Medical Device Regulation (MDR) on biological evaluation of medical devices. The webinar will compare relevant MDR General Safety and Performance Requirements (GSPR) with the Medical Devices Directive (MDD) Essential Requirements; compare MDR GSPR with ISO 10993 and ISO 14971; and discuss the impact of changes in ISO 10993-1:2018 and other ISO standards. A generous Q&A session is planned to accommodate conversation with the speaker—Chairman of ISO/TC 194 Biological Evaluation and Director of Regulatory Consultancy and Quality Assurance at an EU Authorized Representative, regulatory consultancy, and CRO.
Transitioning to Independence Part 2: Best Practices for the Academic Job Hunt
Date and Time: Wednesday, January 22, 2020, 3:00 PM–4:00 PM (ET)
Host: Postdoctoral Assembly (PDA)
Registration is required.
Speakers:
Karen M. Vasquez, PhD
University of Texas at Austin
Patrick Allard, PhD
University of California Los Angeles
Xinxin Ding, PhD
University of Arizona
This webinar series will focus on providing actionable advice on the early career transition to independence and will feature experts with diverse backgrounds, from newly hired assistant professors to members of faculty search committees. The target audience is trainees (postdocs and graduate students), as well as early career investigators.
From the other side of the hiring process, Part 2 will bring together a small panel of academic faculty members who have been on recruiting/hiring committees at different universities. Discussion questions will highlight how to stand out throughout the application process, mistakes in the early application phase, and tips for the on-site interview (dress the part, chalk talk, one-on-one sessions, etc.).
Mechanistic Assessment of Carcinogenicity
Date and Time: Friday, January 24, 2020, 10:00 AM–11:00 AM (ET)
Host: Carcinogenesis Specialty Section (CSS)
Registration is required.
Speaker:
Mirjam Luijten
Rijksinstituut voor Volksgezondheid en Milieu (RIVM)
Presentation Title: Early Mechanistic Key Events for the Prediction of Carcinogenic Potential
While health risks from genotoxic carcinogenic substances can be reliably assessed using genetic toxicity endpoints, risks from substances that induce cancer via other mechanisms (i.e., nongenotoxic carcinogens) remain largely undetected unless a two-year carcinogenicity bioassay is performed. However, the two-year carcinogenicity bioassay involves the use of large numbers of animals, and its results have been scientifically challenged. A transition from the bioassay to a human-relevant framework can provide better predictivity and tests on fewer animals, is more cost-effective, and coincides with our growing knowledge of the mechanistic process of tumor formation. Therefore, a project funded by EPAA, which started in summer 2017, has explored how mode‐of‐action (MOA) information can be used to enhance the prediction of carcinogenic potential (or lack thereof) of agrochemicals. The project aims to select appropriate parameters for MOAs involved in carcinogenesis. For this selection, a review of mechanistic information provided in carcinogenicity reports for ~160 agrochemicals was undertaken. Using this overview, nine MOA networks were identified, including liver enzyme induction, changes to the hormone system, oxidative stress, and sustained cytotoxicity.
Speaker:
Chris Corton, PhD
US EPA
Presentation Title: Transcriptomic Thresholds from Short-Term Assays Predict Rat Liver Tumorigens
Incorporation of quantitative genomic data from short-term rodent studies may adequately define protective thresholds for potential tumorigens as a bridge to move from current testing to greater reliance on in vitro assays. We hypothesized that gene expression biomarkers that measure the activation of the major molecular initiating events (MIEs) in rodent liver cancer adverse outcome pathways exhibit chemical-independent thresholds beyond which cancer occurs and the thresholds could be used to predict liver cancer. The hypothesis was tested by defining thresholds of gene expression biomarkers of liver cancer MIEs using training sets from the 77 and 86 chemicals in the TG-GATES and DrugMatrix datasets, respectively, and testing them in a number of contexts. The biomarkers tested consisting of 7–113 genes included those that predict genotoxicity, cytotoxicity, and activation of AhR, CAR, ER, or PPARα. Thresholds were calculated as the maximum values derived from exposures that do not lead to liver cancer. In all cases, clear threshold values could be identified that were consistent across training and test sets. Thresholds derived from the TG-GATES study were not very predictive of liver tumorigens in the DrugMatrix study (77%–81%). In contrast, thresholds derived from the DrugMatrix study were predictive in the TG-GATES study (84%–100%). The DrugMatrix-derived thresholds were most predictive when applied to test sets of 7d and 14d treatments (100% and 99%, respectively). In addition, thresholds derived from just 12 genes (two/biomarker) exhibited high predictive accuracy (up to 94%). These findings support the idea that early genomic changes can be used to establish threshold estimates or “molecular tipping points” that are predictive of later-life outcomes. (This abstract does not reflect EPA policy.)
NAMs Case Study: Industry/Government Partnerships
Date and Time: Wednesday, January 29, 2020, 11:00 AM–12:30 PM (ET)
Host: In Vitro and Alternative Methods Specialty Section (IVAMSS)
Registration is required.
Speakers:
Monique Perron, ScD
Acting Branch Chief, Risk Assessment Branch IV
US EPA/OPP/HED
Douglas C. Wolf, DVM, PhD, FIATP, ATS
Senior Syngenta Fellow, Product Safety
This webinar will use a case study to discuss the process of leveraging industry/regulatory partnerships to work more efficiently and effectively as we forge ahead in the NAMs space. We will have two speakers, Monique Perron from US EPA and Doug Wolf from Syngenta. The speakers will discuss the processes they took as they worked through an alternative approach to the 90-day inhalation animal study, highlighting key watch-outs and suggestions from their experience.
From Nanomaterials to Advanced Materials: A Health and Safety Perspective
Date and Time: Thursday, January 30, 2020, 1:00 PM–2:00 PM (ET)
Host: Nanoscience and Advanced Materials Specialty Section (NAMSS)
Registration is required.
Speaker:
Dr. Charles Geraci
Associate Director of Emerging Technologies
NIOSH
Advances in nanoscale science have resulted in materials that are more active, more efficient, and more versatile in their commercial applications. A key outgrowth has been the development and deployment of “advanced materials.” These materials are chemically and biologically more active and more efficient for the specific functions for which they are designed. Advanced materials are combining with the development of new manufacturing technologies, such as additive manufacturing, 3D printing, and engineered/synthetic biology, to give us a vision of the new materials, processes, and products that make up “21st-century manufacturing.” The challenge for the EHS professional is to remain current on the issues of potential health hazards, the degree to which these materials are being introduced into new manufacturing technologies, and the way they are used and incorporated into products. The types of risk assessment and management approaches needed to support safe, responsible, and sustainable commercialization of nano- and advanced-material-enabled products can be challenging, but a lot of progress has been made in the past 10 years. Many of the lessons learned with nanotechnology will have direct reapplication opportunities in the rapidly emerging world of advanced materials and the 21st-century manufacturing environment.
US FDA Experience in the Regulatory Application of (Q)SAR Modeling
Date and Time: Wednesday, February 5, 2020, 11:00 AM–12:00 Noon (ET)
Host: Computational Toxicology Specialty Section (CTSS)
Registration is required.
Speaker:
Naomi Kruhlak, PhD
US FDA/CDER
The US Food and Drug Administration (US FDA) actively promotes and supports research into state-of-the-art computational toxicology approaches including (quantitative) structure-activity relationship, also known as(Q)SAR, modeling for regulatory decision-making. Within the US FDA Center for Drug Evaluation and Research, a significant focus of this research is on the safety assessment of drug impurities under the ICH M7 Guideline, where a (Q)SAR prediction can be used as an alternative to empirical testing to assess mutagenic potential. The successful implementation of the ICH M7 Guideline has led to the development of best practices for the conduct of (Q)SAR analyses, evaluation of model outputs, and submission of (Q)SAR data to regulators. Building on this success, new opportunities for the regulatory application of (Q)SARs are being explored for other endpoints, including carcinogenicity and endocrine disruption, as well as for other components of US FDA–regulated products beyond impurities.
This presentation will provide an in-depth look at current regulatory practice and expectations for the use of (Q)SAR models under ICH M7, as well as highlight emerging applications of the methodology to chemical entities and endpoints of regulatory importance to the US FDA.
Challenges and Opportunities in Assessing Health Risk from Unconventional Oil and Gas Development
Date and Time: Wednesday, February 12, 2020, 3:00 PM–4:30 PM (ET)
Host: Risk Assessment Specialty Section (RASS), co-sponsored with the International Society for Exposure Science
Registration is not required.
Speaker:
Donna Voorhees, PhD
Director of Energy Research
Health Effects Institute (HEI)
Boston, MA
Onshore development of oil and natural gas from unconventional resources (unconventional oil and gas development, abbreviated in this presentation as “UOGD”) has expanded rapidly in the United States during the last decade and concern about its potential health effects along with it. While UOGD shares many attributes of conventional oil and gas development that has been around since the 1800s, it is occurring in locations and at a scale not always familiar to those living nearby. This presentation will summarize methodologic challenges and opportunities in understanding the potential for health effects, especially through risk-based analyses.
Beginning in 2012, academic scientists and public health authorities published human health risk assessments and risk-based screening assessments that combined information about potential UOGD-related chemical concentrations with relevant toxicity information to predict risk to communities in Colorado, North Dakota, Pennsylvania and the broader Marcellus region, Texas, and Wyoming. Nearly all assessments quantified risk to community members associated with potential exposure to UOGD-related chemicals in air, but several assessed risks involving water. Assessments varied in their complexity, from screening-level comparisons of chemical concentrations, to health-based benchmarks, to more involved assessments measuring potential exposure specific to a population, including control for baseline, or background, conditions. Conclusions differed among the risk assessments and were subject to important sources of uncertainty about exposure and toxicity and the judgments made by investigators to address them. The body of work also was limited in its relevance to operations, regions, and populations beyond those that were the subject of each assessment. Future investigators must grapple with the extensive temporal and spatial variability in potential exposure as a function of numerous factors (e.g., differences in regulations, environmental conditions, and practices among UOGD operators), the uncertainties about potential exposure (e.g., when and where will operations happen, the identity of chemicals being used, and the efficacy of noise mitigation), and the lack of toxicity information for some chemicals associated with UOGD operations.
Modernization of Cancer Risk Assessment
Date and Time: Wednesday, February 19, 2020, 11:00 AM–12:00 Noon (ET)
Host: Carcinogenesis Specialty Section (CSS)
Registration is required.
Speaker:
Warren Casey, PhD
NIEHS/NTP
Presentation Title: Advances in Carcinogenicity Assessment at the National Toxicology Program
Since the early 1980s, the US National Toxicology Program has served as a national and world resource for conducting the two-year rodent bioassay to assess the (human) carcinogenic potential of industrial and agricultural chemicals, food additives, environmental pollutants, and other exposures of public health concern. However, the acknowledged limitations of the rodent bioassay include high cost, extensive time to conduct and report, and limited translational relevance. In building on its history of innovation, excellence, and impact, the National Toxicology Program is now leading the development of a new framework for assessing human cancer risk from environmental exposures. This talk will discuss the approaches being developed to better understand and interrogate the initiation/promotion and progression processes of human carcinogenesis as well as the etiology of a set of human cancers potentially associated with environmental exposures. The rationale for selecting these specific cancer targets and progress made on developing the associated adverse outcome pathways will be discussed. Other topics covered will include a description of ongoing efforts to develop a suite of in vivo, in vitro, and in silico approaches to screen and prioritize substances, utilization of longitudinal human cancer data, and opportunities for future engagement with stakeholders.
Speaker:
Sabitha Papineni, DVM, PhD
Corteva Agriscience
Presentation Title: ReCAAP—Carcinogenicity Case Study Waivers for Food-Use Pesticide Registration
Reviews of the rodent cancer bioassay over the past 40 years have raised questions about its relevance and regulatory need to assess risk to human health. As a result, a working group composed of experts from government, industry, and nongovernment organizations has formed the Rethinking Carcinogenicity Assessment for Agrochemicals Project (ReCAAP) to evaluate the appropriateness of waiving rodent bioassays for the registration of food-use pesticides. This presentation will provide case study examples of carcinogenicity waivers formulated through a weight-of-evidence-based (WoE) approach. The WoE includes information on pesticide exposure, mode of action, physiochemical properties, and subchronic toxicological data from defined endpoints. The results of these WoE reviews will be used to establish the criteria for when the mouse and/or rat cancer bioassay can be waived with sufficient confidence to protect public health.
Transitioning to Independence Webinar Series Part 3: How to Get the Most out of Your Mentoring Relationships
Date and Time: Wednesday, February 26, 2020, 12:00 Noon–1:00 PM (ET)
Host: Postdoctoral Assembly (PDA)
Registration is required.
Speakers:
Laura Van Winkle, PhD
University of California Davis
Debra Laskin, PhD
Rutgers, The State University of New Jersey
John Wise, PhD
University of Louisville
This webinar series will focus on providing actionable advice on the early career transition to independence and will feature experts with diverse backgrounds, from newly hired assistant professors to members of faculty search committees. The target audience is trainees (postdocs and graduate students), as well as early career investigators.
This webinar will feature experienced faculty members who can provide input on mentoring issues and how to seek advice throughout your career, even as you transition to independence. The primary learning objectives will be (1) how to maintain mentoring relationships during the transition to independence, especially while trying to distinguish yourself from your mentor/PI; and (2) how to become a good mentor—while still junior yourself—as you build your lab and advise others from the role of PI. Moderator-led discussion will feature perspectives from three academic career stages (graduate student, postdoc, and Assistant Professor).