ESTIV organizes free webinars on a monthly basis together with the American Society for Cellular and Computational Toxicology (ASCCT). These webinars cover a broad spectrum of topics relevant to the fields of in vitro and in silico toxicology. ESTIV members are welcome to propose topics and speakers at any time. All webinars are recorded, archived and available for ESTIV members.
Estiv and ASCCT Webinars are available for all to attend and watch at no cost.
Webinars – 2020
April 30, 2020 – Use of New Approach Methodologies for cosmetic safety assessment without animal testing
Thursday, Apr 30, 2020
11:00 AM US ET / 17:00 CET
Recent advances in chemical safety assessment now allow the complete evaluation of personal care products without the use of animals. Exposure based approaches and hypothesis-driven data generation form the basis of non-animal cosmetic safety assessments. The safety assessment approach begins with problem formulation and evaluation of existing information before considering the development of targeted testing approaches. Assessment tools, often described as New Approach Methodologies (NAMs), can include computational models and human-relevant in vitro assays which are applied in combination to provide information on ingredient hazard and risk assessment. Finally, these disparate types of information are integrated and weighted in a transparent assessment that captures uncertainty. Each presentation in this webinar will cover different aspects of this decision process.
11:00 Introduction: Hypothesis led safety assessment of cosmetics,
Catherine Willett, Humane Society International
11:10 Exposure based safety assessment of cosmetics,
Corie Ellison, Procter and Gamble
11:25 The application of in silico models to support decision making in toxicology: QSAR, informatics, pathway modelling, uncertainty,
Chris Barber, Lhasa, LTD
11:40 In vitro approaches to cosmetic safety assessment
Paul Walker, Cyprotex Discovery Ltd
11:55 Integration of new approach methodologies for cosmetic safety decision making
Matt Dent, Unilever
11:10 Q & A
For more information about the project, see AFSAcollaboration.org/Cosmetics
March 11th, 2020 – ASCCT Award Winners Webinar – Toxicological mechanistic inference: Generating mechanistic explanations of adverse outcomes
Wednesday, March 11th, 2020
11:00 AM US ET / 17:00 CET
Presenter: Ignacio J. Tripodi, PhD Candidate in Computer Science / Interdisciplinary Quantitative Biology, University of Colorado, Boulder
Registration Link: https://attendee.gotowebinar.com/register/9200492703200567307
Government regulators and others concerned about toxic chemicals in the environment hold that a mechanistic, causal explanation of a mechanism of toxicity is strongly preferred over a statistical or machine learning-based prediction by itself. We thus present a mechanistic inference framework, which can generate hypotheses of the most likely mechanisms of toxicity for a specific chemical and cell type, using gene expression time series on human tissue and a semantically-interconnected knowledge graph. We seek enrichment in our manually-curated list of high-level mechanisms of toxicity (e.g. “Triggering of caspase-mediated apoptosis via release of cytochrome C”, or “Mitochondria-mediated toxicity by inhibition of electron transport chain”), represented as causally-linked Gene Ontology concepts.
Our knowledge representation is an extension of the PheKnowLator knowledge graph. It consists of an integration of concepts from multiple ontologies (GO, PRO, HPO, ChEBI, PATO, DOID, CL), as well as relevant concepts from Reactome, Uniprot, the cellular toxicogenomics database (CTD), and the AOP Wiki. The expression assays were obtained from the Open TG-Gates, CarcinoGenomics, and other projects, consisting of human liver, kidney, and lung, bronchial, buccal, and nasal epithelial cells exposed to a sizeable number of chemicals that elicit different mechanisms of toxicity. Both our knowledge graph and experimental transcriptomics data are human-centric. Besides predicting the most likely mechanisms of toxicity from the transcriptomics assays, we generate putative explanations based on the most significant genes at each time point with known links to their corresponding mechanism steps. This provides a transparent, possible explanation for the mechanisms of toxicity, that would help a researcher’s decision-making process and aid further experimental design. Furthermore, we were able to experimentally validate our mechanistic predictions for some chemicals without an established mechanism of toxicity.
Co-expression Network Analysis to Identify Heterogeneity Between the Breast Cancer Cell Line MCF-7 and Human Breast Cancer Tissues
February 25th, 2020 – Moving away from animal testing for acute inhalation toxicity testing
Tuesday, February 25th, 2020
10:00 AM US ET / 17:00 CET
Presented by Emilie Da Silva, PhD student, Technical University of Denmark/National Research Center for the Working Environment, Denmark
Registration Link: https://attendee.gotowebinar.com/register/4278909332419455243
ABSTRACT: Testing for acute inhalation toxicity is required for chemicals manufactured or imported at tonnages ≥ 10 tons per year (Commission Regulation (EC) No 440/2008) and for biocides (Regulation (EU) No 528/2012) and plant protection products (Regulation (EU) No 283/2013) before they are allowed on the market. Currently, three OECD Test Guidelines are available (TG 403, TG 436, and TG 433), all based on the exposure of rodents to the substance of interest for up to 4 hours. The use of animals for toxicological evaluation does not come without challenges. Animal experiments are costly and time consuming. It is estimated that the turnaround time for carrying out an acute inhalation test is 3 to 4 months. Besides, using rodents in order to predict the toxicity of a compound in humans is arguable given the differences in the features of the respiratory tract. The development and the validation of alternative methods in chemico, in vitro and/or in silico are needed. To do so, the mechanistic understanding of the toxicity of inhaled chemicals is key.
An innovative in vitro method for acute inhalation toxicity will be presented. This cell-free method is based on the monitoring of lung surfactant function. Indeed, the lung surfactant layer in the alveoli is the first barrier that inhaled compounds will encounter when they reach the respiratory region in the lungs. The correlation between the inhibition of the lung surfactant function and the decrease in tidal volume in mice was shown with a variety of compounds including excipients for drug formulation, and impregnation spray products. During this webinar, the method will be introduced and explained, and case studies using different chemical groups will be presented.
January 21, 2020 – ESTIV Award Winners Webinar – Role of In Vitro Mechanistic Data for the Assessment of Endocrine Disruptors in the Regulatory Context
Presented by Dr. Laura Escrivá, Assistant Professor, University of Valencia, Spain.
Tuesday, January 21st, 2020 at 4:00 pm CET
Available online at: https://www.ascctox.org/webinars/eVmBMbpCMaG5/61
ABSTRACT: Scientific EU criteria and guidance from ECHA and EFSA to identify substances with Endocrine Disruptor (ED) properties have recently been implemented for plant protection products and biocidal products. The ECHA/EFSA guidance, mainly addressing EATS (estrogen, androgen, thyroid, steridogenesis) modalities, provides a protocol for ED identification, which includes the evaluation of both the adverse effects and the endocrine activity, by applying weight of evidence analysis.
The assessment of the endocrine activity requires in vitro mechanistic data providing information on the mechanism through which a substance could be considered endocrine active (e.g. by binding to and activating a receptor or interfering with hormone production). Moreover, when potentially endocrine-related adverse effects and endocrine activity are identified, the biological plausibility of the link between endocrine activity and the endocrine mediated adversity should be established by a mode of action analysis. The webinar will focus on the different steps for ED identification according to the ECHA/EFSA guidance illustrating how essential it is the in vitro data for ED assessment under EU regulatory context.
January 21, 2020 – ESTIV Award Winners Webinar – A battery of animal-free in vitro assays for evaluating prenatal developmental toxicity potency of highly complex petroleum substances
Presented by Dr. Lenny Kamelia, Division of Toxicology, Wageningen University and Research, The Netherlands.
Tuesday, January 21st, 2020 at 4:00 pm CET
Available online at: https://www.ascctox.org/webinars/eVmBMbpCMaG5/61
ABSTRACT: REACH legislation requires prenatal developmental toxicity (PDT) testing for substances registered at a volume of >100 tonnes/year, which also applies to petroleum substances (PS). Given that i) PDT testing is one of the most complex, and animal- and resource-intensive regulatory requirements for substances produced at >100 tonnes/year, and ii) PS are highly complex materials (UVCBs), the development of alternative non-animal based testing strategies for PS poses huge challenges. Some PS contain high concentrations of polycyclic aromatic hydrocarbons (PAHs) and we hypothesize that PDT as observed for some PS is caused by certain types of PAH present in these products. To this purpose, DMSO-extracts of 9 PS (varying in PAH content; from 5 different product categories), 1 highly refined base oil (HRBO) (containing no PAHs), and 2 gas-to-liquid (GTL) products (devoid of PAHs) were tested in a battery of in vitro assays, including the embryonic stem cell test (EST), the zebrafish embryotoxicity test (ZET), and the aryl hydrocarbon (AhR) CALUX assay. All DMSO-extracts of the PS, but not of the HRBO and GTL, induced concentration-dependent PDT as quantified in the EST and ZET, with their potency being proportional to their 3- to 7-ring PAH content. Moreover, all PS extracts also showed AhR-mediated activity in the AhR CALUX assay, suggesting a role of the AhR in mediating the observed PDT by these substances. Combining the results of the EST, ZET, AhR CALUX assay, and the PAH content, ranked and clustered the test compounds in line with their in vivo PDT potencies. In conclusion, our battery of in vitro assays, consisting of the EST, ZET and AhR CALUX assay, is able to evaluate and differentiate the PDT potency of highly complex PS, within and among categories. The results are also in concordance with our hypothesis on the role of specific groups of PAHs present in some PS for the observed PDT induced by these substances.
Archived Webinars – 2019
Deep Learning in Toxicity Prediction: Reasons for Use and Possible Applications
Presented by Dr. Suman Chakravarti, Chief Scientific Officer, MultiCASE
December 4, 2019 at 4:00 pm CET
ABSTRACT: Use of deep learning is increasing in solving different problems in computational toxicology and QSAR methodology in general. However, it is important to recognize the strengths of deep learning techniques in order to get the best out of them.
This webinar will focus on different aspects of computational toxicity assessments that can be improved using deep learning techniques beyond just increasing the accuracy of the predictions. For example, building scalable QSARs using big data, eliminating the use of precomputed descriptors from QSARs, expanding domain of applicability of QSARs and identification of toxicity alerts using deep learning techniques. In addition, available free tools and different types of deep learning architectures that are relevant to toxicity assessments will be discussed with the aid of case studies.
December 4th Webinar, Deep Learning in Toxicity Prediction: Reasons for Use and Possible Applications, presented by Suman Chakravarti, Chief Scientific Officer, MultiCASE, has been posted online and is now available for viewing at your convenience.
The pros and cons of 3D in vitro cultures of liver fibrosis
Presented by Leo van Grunsven, Vrije Universiteit Brussel.
November 4, 2019 at 4:00 pm CET
ABSTRACT: Chronic liver disease is the major cause of progressive liver fibrosis which, in turn, leads to cirrhosis of the liver. One major obstacle in the development of efficient therapies is the lack of robust and representative in vitro models of human liver fibrosis to aid in understanding the basic mechanisms of the disease and in the development phase of pharmaceuticals. The aim of this presentation is to give some background on the mechanisms involved in liver fibrosis development and why our work is based on the central hypothesis that liver fibrosis in vitro cannot be studied using only hepatic stellate cells (HSCs)–the main producer of scar tissue during fibrosis. I will present and discuss some results and problems we faced while developing an in vitro liver fibrosis model. We established a model in which HepaRG cells (Biopredic) were co-cultured with either in-house isolated HSCs or in-house differentiated induced pluripotent stem cell derived HSCs. In both cases, exposure to hepatotoxins resulted in hepatocytic damage and consequent HSC activation. We now work on a model using only primary mouse HSCs and hepatocytes. I will also discuss some of our work aiming at developing more complex primary mouse co-cultures for liver disease modeling and briefly address the work of other groups that reported on such complex in vitro culture systems.
The November 4th Webinar, The pros and cons of 3D in vitro culture models of liver fibrosis, presented Prof. Leo A. van Grunsven, Vrije Universiteit Brussel, has been posted online and is now available for viewing at your convenience.
Translational challenges in in vitro nephrotoxicity model
Presented by Roos Masereeuw, Div. Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
October 22, 2019 at 4:00 pm CET
ABSTRACT: Adverse effects caused by exposure to foreign compounds, including drugs, often involve the kidney. In fact, 14 to 26% of the acute kidney injury events reported can be related to drug-induced kidney injury. Although acute damage to the kidney may be reversible, depending on severity, 30% of the patients develop structural renal dysfunction leading to chronic kidney disease eventually progressing into end-stage kidney disease. Early prediction of adverse effects such as drug interactions and renal toxicity is therefore imperative for clinical practice and for the development of new and safe drugs. Current in vitro assays do not accurately allow such prediction, predominantly due to inadequate preservation of the organs’ microenvironment. The kidney epithelium is highly polarized, and the maintenance of this polarity is critical for optimal functioning and responsiveness to environmental signals influencing cell proliferation, migration and differentiation. This presentation will provide an overview of advances in 3D cultures of human renal cells and organoids in microfluidics, and in particular kidney tubules, thereby improving physiological performance of the tissue. These microphysiological systems have great potential for drug screenings and provide novel alternative strategies for the prediction of renal drug disposition and safety assessment in a human-specific context. However, knowledge gaps in quantitative translation of renal drug disposition from microphysiological systems still exist and will be discussed.
Developmental neurotoxicity evaluation: on the road to regulatory acceptance
Presented by Prof. Ellen Fritsche, Leibniz Research Institute for Environmental Medicine-Germany
August 28, 2019 at 4:00 PM CET
Nerve-on-a-chip platform for assessing chemotherapy-induced peripheral neuropathy
Presented by Dr. Lowry Curley, AxoSim Inc.
September 17, 2019 at 5:00 PM CET:
Using Quantitative Systems Toxicology (QST): Improving the safety of drugs while reducing animal testing (July 2019) Presenter: Paul B. Watkins, M.D., University of North Carolina – Chapel Hill
GARD™air – An in vitro assay to test for respiratory sensitizers using genomic biomarkers and machine learning (June 2019) Presenter: Joshua Schmidt, SenzaGen Inc., USA Co-author: Andy Forreryd, SenzaGen AB, Lund, Sweden
EPA computational tools (May 2019)
The CompTox Chemicals Dashboard and Generalized Read Across
Presenters: Antony Williams and Grace Patlewicz, EPA
Automated and Integrated Analysis Workflow for Adverse Outcome Pathway Identification, Hypothesis Generation and Risk Assessment (April 2019) Presenters:
Noffisat O. Oki (1) and Tatyana Doktorova (2)
1Edelweiss Connect Inc, Durham, NC, USA
2Edelweiss Connect Gmbh, Basel, Switzerland
Advancing tools for predictive toxicology (March 2019) Title: Establishment of bile duct tubular structure mimicking the intrahepatic bile duct morphogenesis for an in vitro bile recovery
Presenters: Astia Rizki-‐Safitri, Marie Shinohara, Minoru Tanaka, and Yasuyuki Sakai
Title: Generation of recombinant human anti-diphtheria toxin neutralizing antibody to replace equine sera
Presenters: Esther Wenzel, Paul Stickings, Jeffrey Brown, Thea Sesardic, Androulla Efstratiou, Michael Hust
Title: Development and Use of Adverse Outcome Pathway (AOP) Networks to Support Assessment of Organ Level Effects
Presenters: Nicoleta Spinu, Mark TD Cronin, Steven J. Enoch, and Judith C Madden
Combining biological and computational approaches (February 2019) Presenter 1: Daniel Russo, Rutgers University
Title: Developing Mechanism-Based Animal Toxicity Models: A Chemocentric Approach Using Big Data
Presenter 2: Sudin Bhattacharya, Michigan State University
Title: Integrating Genomics and Epigenomics into Predictive Toxicology of the AH Receptor
Nanoceramic pulmonary toxicity & reproducible cell line technology (January 2019)
Award Winners Series: Nanoceramic pulmonary toxicity & reproducible cell line technology
Jan 23, 2019 10:00 AM EST
Presenter 1: Maria João Bessa, PhD candidate, Portuguese National Institute of Health
Title: Pairwise toxicity evaluation of ceramic nanoparticles exposure in human alveolar epithelial A549 cells at submerged and air-liquid cultures
Presenter 2: Tom Wahlicht, PhD, InSCREENeX GmbH
Title: Reproducible in vitro toxicology testing using functional immortalized cells