Scientific Program

IUTOX 15th International Congress of Toxicology, Co-Hosted by SOT

Click the > symbol to see more information on a specific session.

Symposia

Tuesday, July 16, 2019

9:00 AM–11:00 AM

SYM01: Emerging Mechanisms of Chemical Teratogenesis

Room 312

Chairperson(s): Peter G. Wells, University of Toronto; and Neil Vargesson, University of Aberdeen.

By age 5, 12–14% of children show problems of developmental origin (teratogenesis) including structural malformations, infant mortality and functional deficits like neurodevelopmental disorders. In utero exposure to drugs and environmental chemicals (xenobiotics) is estimated to cause about 5% of malformations detected at birth, and a higher percentage of postnatal functional disorders. Current associations are likely underestimates due to detection limitations and dependence upon interactions with genetic/epigenetic factors. This symposium presents emerging data from animal models and humans revealing mechanisms that underlie these disorders and determine individual risk. The first speaker will discuss the involvement of reactive oxygen species, DNA oxidation and repair in neurodevelopmental deficits initiated by fetal exposure to methamphetamine and alcohol (ethanol). The second speaker will discuss the role of stress response signaling pathways, and particularly the P53 pathway, in abnormal embryonic development caused by cyclophosphamide and hydroxyurea. The third speaker will focus upon epigenetic mechanisms, and particularly microRNAs (miRNAs), in humans and human trophoblast cell lines, in ethanol teratogenesis. The final speaker will discuss the vascular basis of teratogenesis exemplified by thalidomide. Insights from these studies may facilitate the development of diagnostic biomarkers for high-risk individuals, and novel strategies for therapeutic mitigation.

Oxidative DNA Damage and Repair in Teratogenesis. Peter G. Wells, University of Toronto, Canada.

Stress-Response Signaling Pathways in the Organogenesis-Stage Embryo. Barbara F. Hales, McGill University, Canada.

Assessing the Function of Endocrine miRNAs in Pregnant Women That Predict FASD Infant Outcomes. Rajesh C. Miranda, Texas A&M Health Science Center, The United States of America.

Vascular Basis of Teratogenesis. Neil Vargesson, University of Aberdeen, United Kingdom.

SYM02: International Efforts to Ensure Global Food Safety: Incorporating Advanced Toxicological Sciences in Food Risk Assessment

Room 316

Chairperson(s): Angelika Tritscher, World Health Organization; and Yongxiang Fan, China National Centre for Food Safety Risk Assessment.

Science-based food standards are essential to protecting public health and facilitating international food trade. To assist the Codex Alimentarius Commission to establish international standards for food additives, chemical contaminants, veterinary drug residues and pesticide residues, the Food and Agriculture Organization of the United Nations (FAO) and World Health Organization (WHO) regularly convene joint expert committees on Food Additives (JECFA) and joint meetings on pesticide residues (JMPR) to assess the health risk of exposures to these chemicals from food. Another important element of this work is the update and harmonization of risk assessment methods and principles as science evolves, and the development of interactive tools and databases to assist food chemical risk assessment and management globally. In this symposium, WHO and experts involved in this international work will present recent efforts and new developments initiated by JECFA and JMPR that reflect the implementing of current science. Toxicologists who have served on these international committees will give their perspectives and share examples that showcase how advances in toxicological sciences improve the quality and rigor of food chemical risk assessments. This symposium intends to enhance awareness, share knowledge and encourage participation among the international toxicology and risk assessment community.

Risk Assessment Methodologies As Applied by JECFA and JMPR. Angelika Tritscher, World Health Organization, Switzerland.

Applications of Evolving Science in Assessing the Safety of Food Additives and Chemical Contaminants by JECFA. Yu Janet Zang, US Food and Drug Administration, The United States of America.

Incorporation of Duration of Exposure into The Risk Assessment of Residues of Pesticides and Veterinary Drugs in Food. Alan Boobis, Imperial College London, United Kingdom.

Updated WHO Guidance on the Evaluation of Genotoxicity of Compounds in Food. Virunya Bhat, NSF International, The United States of America.

SYM03: Lysosomes: Key Regulators of Inflammation and Life or Death of a Cell

Room 313

Chairperson(s): Andrij Holian, The University of Montana; and Srikanth Nadadur, National Institute of Environmental Health Sciences.

Lysosomes are important organelles involved in the maintenance of cellular homeostasis and degrading extracellular pathogens and antigen presentation. It is now recognized that lysosomes also play a critical role in fundamental cellular processes, such as protein secretion, endocytic receptor recycling, energy metabolism, and cell signaling. Lysosomes are also involved in the degradation of cellular components through the process of autophagy as homeostatic pathways for normal cells. The lysosomal membrane is protected from the acidic hydrolases by lysosome specific expression of membrane proteins such as Lamp-1 and Lamp-2. However, in response to certain toxic stimuli, lysosomal membrane permeabilization (LMP) may occur causing NLRP3 inflammasome activation, alteration of normal autophagy, etc., leading to the initiation of intracellular pathways resulting in inflammation, fibrosis and cancer. Therefore, an understanding of the regulation of lysosomal membrane integrity is therefore essential in preventing the release of hydrolytic enzymes to the cytosol which would affect normal cell function and likely involved in a number of chronic diseases. This symposium will review current information on the role of this important organelle in normal cellular function, as well as, potential mechanisms leading to LMP resulting in cell death and inflammation.

Mechanistic Insights in Lysosome-Mediated Cell Death. Karin Öllinger, Linköping University, Sweden.

Lysosomal Alterations in Health and Disease. Patricia Boya, Centro de Investigaciones Biologicas, CIB-CSIC, Spain.

Impact of Lipids and Particles on Lysosomal Membrane Permeability (LMP). Andrij Holian, University of Montana, The United States of America.

Why Lysosomal Membrane Permeabilization (LMP) Could Be Considered a Key Event (KE) in Adverse Outcome Pathway (AOP) to Particle-Induced Inflammation and Fibrosis of the Lung. Mary Gulumian, Toxicology Resaerch Projects NIOH, South Africa.

SYM04: Systemic and Functional Impacts of Maternal Pulmonary Nanomaterial Exposures on the Offspring

Room 315

Chairperson(s): Phoebe Stapleton, Rutgers University; and Karin Sørig Hougaard, National Research Centre for the Working Environment.

Toxicological exposures during gestation often results in outward teratogenicity, malformations, and fetal death. Recently xenobiotic exposures have been found to induce subtle teratogenic responses in the fetus and long lasting effects in the offspring. The effects of nanomaterial exposure are still poorly understood, and even more so for the shaping of fetal physiology. Recent studies point towards fetal multi-organ sensitivity to maternal particle exposure during pregnancy. This symposium will focus on how xenobiotic engineered nanomaterial exposures during susceptible gestational time points can affect the health of the developing offspring. These presentations will demonstrate exposure to engineered nanomaterials during gestation may compromise the in utero environment. Fetal impairments may be associated with particle translocation and direct placental toxicity. Maternal exposures have led to severe consequences on the fetal and adult physiological function of the pulmonary, neurological, reproductive, and cardiovascular systems. Lastly, maternal exposures can lead to epigenetic alterations in the fetal genome leading to modifications of gene expression. In summary, this symposium seeks to address the significant threats that engineered nanomaterial exposure during gestation may impose to alter fetal developmental trajectory towards suboptimal physiological phenotypes and identify how future research may enlighten our insight within the field of developmental nanotoxicology.

Inhalation of Nanomaterials Can Result in Systemic Effects Leading to Pre- and Postnatal Effects. Flemming R. Cassee, National Institute for Public Health and the Environment (RIVM), The Netherlands.

Deposition of Nanomaterials at the Feto-Maternal Interphase and Their Effects on the Fetus. Luisa Campagnolo, University of Rome “Tor Vergata”, Italy.

Effects of Maternal Lung Exposure to Nanomaterials on the Nervous and Male Reproductive Systems. Karin Sørig Hougaard, National Research Centre for the Working Environment, Denmark.

Cardiovascular, Metabolic, and Epigenetic Susceptibility in Offspring after Maternal Engineered Nanomaterial Exposure. Phoebe Stapleton, Rutgers University, The United States of America.

2:30 PM–4:30 PM

SYM05: Concerns of Herbal Product-Induced Toxicity

Room 315

Chairperson(s): Nan Mei, US FDA, National Center for Toxicological Research; and Amy C. Brown, John A. Burns School of Medicine, University of Hawaii at Manoa.

Global interest in botanicals or derivative products is growing because people often believe that “natural” sources may be beneficial to health. Herbal products made from botanicals are usually used to maintain or improve health. A group of chemicals can be isolated from a botanical and sold as a botanical dietary supplement. Thousands of herbal products are sold in many forms and millions of people worldwide regularly consume herbal products. Herbal products are expected to be safe, effective, and of appropriate quality. However, the complex chemical nature of herbal products makes it difficult for efficacy and safety evaluation. Herbal products often exhibit great variability in quality because of problems in authentication, adulteration and substitution, along with numerous variable factors during growth, harvest, and postharvest processing. Reported adverse effects have raised public health risk concerns regarding the concentration, composition, and individual contaminants of dietary supplements. Recently, the IARC has assessed the carcinogenicity of some herbal products, and part of them are classified as Group 2B (volume 108 of the IARC Monographs). Herbal products also have been recognized in certain cases of drug-induced liver injury. Therefore, testing of herbal products for efficacy and safety is important and needs to be conducted scientifically.

Safety Evaluation of Herbal Products: Current Standards to a Proposed More Comprehensive Evaluation. Ahmet Aydın, Yeditepe University, Turkey.

Hepatotoxicity of Usnic Acid and Its Mechanisms. Si Chen, National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA), The United States of America.

Neurotoxicity of Ginkgo biloba Seeds and Its Mechanisms. Daisuke Kobayashi, Health Sciences University of Hokkaido, Japan.

Cardiotoxicity of Aconitum Plants and Its Mechanisms. Xianju Huang, South-Central University for Nationalities, China.

SYM06: Emerging CRISPR Applications in Environmental Health Sciences and Toxicology

Room 313

Chairperson(s): Luoping Zhang, University of California, Berkeley; and Chris Vulpe, University of Florida.

Advanced genome editing technology, most notably the CRISPR-Cas system, has been rapidly applied to numerous fields, including gene-therapy for treatment of human diseases, drug screening and development, and plant engineering to improve food security. Contrary to its widespread interdisciplinary use, CRISPR application in environmental health science and toxicology has remained limited. Similar to drug screens, toxicity of environmental chemicals can be readily tested in a cell-based assay and their mechanistic pathways can be further elucidated through genome-wide functional testing. Previously, this approach was applied in a yeast screening system, and findings were validated in human cells in vitro and in population studies. To date, the novel CRISPR technology, including genome-wide CRISPRi (interference, loss-of-function) and CRISPRa (activation, gain-of-function) can be employed to fully examine genomic responses to a tested chemical. Recently, a targeted approach, Tox-CRISPR, is developed to focus on testing genes frequently involved in toxicity caused by environmental exposures. Applying both genome-wide and targeted approaches, we can harness the power and flexibility of the CRISPR functional screening to gain mechanistic insight in modern toxicology for an unprecedented protection of human and environmental health. This symposium aims to guild and encourage ICT community to apply CRISPR in environmental health research.

Genome-Wide and Targeted CRISPR Screening to Understand Gene-Environment Interactions. Chris Vulpe, University of Florida, The United States of America.

CRISPR Screening to Identify Suppressors of Cellular Stress Response to Proteo-Toxicants. Quan Lu, School of Public Health, Harvard University, The United States of America.

CRISPR Application to Uncover Redox Biology. Navdeep Chandel, School of Medicine, Northwestern University, The United States of America.

A Vision for CRISPR Applications in Toxicology and Environmental Health. Luoping Zhang, School of Public Health, University of California, Berkeley, The United States of America.

SYM07: Epigenetic Biomarkers of Exposure to Environmental Carcinogens

Room 312

Chairperson(s): Igor Pogribny, National Center for Toxicological Research.

Cancer development in humans is determined by the interaction of two key etiological factors, genetics and environmental exposures. There is increasing evidence, however, that genetic factors might not be the principal cause of cancer development, but that exposure to natural and man-made chemical and physical carcinogens may have a more profound impact. Extensive and constantly growing data indicate that epigenome is a major target for environmental carcinogens and is greatly affected by their exposure. This suggests that carcinogen-induced epigenetic changes might be useful in safety assessment of carcinogens, including pharmaceutical products and food additives and contaminants. Furthermore, the transition from using epigenetic signatures of exposure as potential biomarkers only to identifying their mechanistic role in cancer development allows for better characterization and fundamental understanding of the biology of how environmental insults are involved in the carcinogenic process. This symposium will present current knowledge on the linkages among exposure, genome, epigenome and cutting-edge research on the role of the epigenome as a central component linking environmental exposures to cancer development. Additionally, it will illustrate that the evaluation of carcinogen-induced epigenomic alterations may not only enhance the carcinogen assessment process but also provide opportunity for the development of better cancer preventive strategies.

Epigenetic Mechanisms and Cancer: An Interface between the Environment and the Genome. Zdenko Herceg, International Research on Cancer, France.

Epigenomics and Drug-Induced Carcinogenicity. Jonathan Moggs, Novartis Institutes for BioMedical Research, Switzerland.

The Role of Epigenetic Science in Carcinogen Detection. Igor Pogribny, National Center for Toxicological Research, The United States of America.

Epigenetic Mechanism of Chromium-Induced Cell Transformation and Tumorigenesis. Chengfeng Yang, Department of Toxicology and Cancer Biology, University of Kentucky, The United States of America.

SYM08: New Approach Methodologies: A Global Perspective

Room 316

Chairperson(s): Charu Chandrasekera, Canadian Centre for Alternatives to Animal Methods/Validation of Alternative Methods (CaCVAM); and Nicole Kleinstreuer, The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods.

From the Americas to the Far East, countries across the globe have established national Centers for the Validation of Alternatives Methods (CVAMs) dedicated to the development, validation, and promotion of non-animal alternative methods that can reduce and replace the current—predominantly animal based—modes of toxicological risk assessment. These integrative new approach methodologies offer rapid, human-relevant predictions, enabling research and regulatory enterprises to streamline safety and risk assessment. Promising new technologies across the spectrum—from molecular and cellular in vitro alternatives to microphysiological systems to systems biology and computational toxicology—are poised to improve the reliability, reproducibility, sensitivity, and human relevance of assessing both toxicity and efficacy. In keeping with the theme for IUTOX 2019—to create diverse sessions highlighting excellence in science and toxicology from across the globe—here we present the latest 21st century toxicology and regulatory testing efforts from three continents: Americas (USA and Canada), European Union, and Asia (Japan). These members of the International Cooperation on Alternative Test Methods (ICATM) representing academic, government, and regulatory sectors will discuss their respective strategies, projects, and global harmonization efforts.

Beyond the Silver Anniversary: The Next 25 Years of Alternatives in the European Union. Maurice Whelan, European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), European Commission Joint Research Centre, Italy.

Adopting New Approach Methodologies: The US Strategic Roadmap and Implementation Activities. Nicole Kleinstreuer, The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, The United States of America.

21st Century Toxicology and Regulatory Testing: An Update from East Asia. Hajime Kojima, Japanese Center for the Validation of Alternative Methods (JaCVAM), National Institute of Health Sciences, Japan.

O Canada: A Strategic Vision toward Replacement in the True North. Charu Chandrasekera, Canadian Centre for Alternatives to Animal Methods/Validation of Alternative Methods (CaCVAM), Canada.

Wednesday, July 17, 2019

9:00 AM–11:00 AM

SYM09: Clinical and Mechanistic Aspects of Drug-Induced Liver Injury

Room 316

Chairperson(s): José E. Manautou, University of Connecticut; and Ann Daly, Institute of Cellular Medicine.

Drug-induced liver injury (DILI) continues to be prominent problem in drug development and patient care. Although our knowledge of DILI mechanisms is incomplete, multiple cellular events and their molecular mediators contributing to DILI have been defined. Despite multiple efforts, preclinical animal models do not always predict liver injury in humans. This has prompted investigators to develop new and better screening tools and to identify new genetic determinants of DILI earlier in the drug discovery process. This symposium will cover the various DILI risk factors relating to immune response, including HLA alleles, followed by the impact of drug transporters on compensatory hepatocellular regeneration following liver injury and the establishment of new animal models to study DILI by acyl glucuronide intermediates. We will conclude the symposium with a description of efforts by world-wide registries and multicenter networks in identifying mechanistic-based DILI biomarkers and the use of ‘omics approaches to the study DILI.

Genetic Aspects of DILI: Recent Advances on Predicting Risk. Ann K. Daly, Institute of Cellular Medicine, Newcastle University, United Kingdom.

Application of Circulating MicroRNA to Diagnose Early Stage of Liver Injury and Its Pathogenesis in Rat DILI Model. Tsuyoshi Yokoi, Nagoya University Graduate School of Medicine, Japan.

Impact of Multidrug Resistance Protein 4 (MRP4/ABCC4) Function in Compensatory Hepatocellular Proliferation. José E. Manautou, University of Connecticut, The United States of America.

Clinical and Mechanistic Aspects of Drug-Induced Liver Injury. Fernando Bessone, University of Rosario School of Medicine, Argentina.

SYM10: Effects of Environmental Mixture Exposure on Brain Development and Function Based on Epidemiological, In Vivo, and In Vitro Studies

Room 313

Chairperson(s): Anna Bal-Price, European Commission Joint Research Centre (JRC); and Oddvar Myhre, Norwegian Institute of Public Health, Department of Toxicology and Risk Assessment.

Epidemiological and experimental data suggest that pre- and postnatal exposure towards chemical mixtures affects brain development. In addition to genetic factors, such exposure might be causally linked to the recently increased prevalence of neurodevelopmental disorders (NDDs) like attention deficit/hyperactivity disorder, autism spectrum disorders and learning disabilities. Yet, there is a profound knowledge gap in understanding the chemical-related pathogenesis of NDDs. Therefore, novel approaches in human exposure assessment, in vitro and in vivo studies are needed to identify such causative factors. Speakers of this session will present from the scientific and regulatory point of views the most recent approaches (a) on evaluation and description of an alternative developmental neurotoxicity testing battery permitting (b) evaluation of an impact of mixture exposure on brain development using in vitro approaches, driven by key events identified in relevant adverse outcome pathways, as well as (c) a mixture risk assessment of combined human exposures to PBDEs and (d) identification of possible mechanisms of chemical mixtures as risk factors for NDDs based on epidemiological and in vivo studies. As NDDs have profound consequences for families and society, the identification of preventable risk factors such as environmental pollution exposure should be of high priority.

Methods for Stage-Specific Developmental Neurotoxicity Testing with Human Stem-/Progenitor Cell-Based Models for Mixture Evaluation. Ellen Fritsche, IUF, Leibniz Research Institute for Environmental Medicine, Germany.

Adverse Outcome Pathways (AOPs)-Driven Evaluation of Developmental Neurotoxicity Induced by Mixture of Environmental Chemicals. Anna Bal-Price, European Commission Joint Research Centre (JRC), Italy.

Mechanisms of Environmental Pollutants Mixtures As Risk Factor for Attention Deficit/Hyperactivity Disorder and Autism Pathophysiology Based on Epidemiological and In Vivo Studies. Oddvar Myhre, Norwegian Institute of Public Health, Department of Toxicology and Risk Assessment, Norway.

A Human Mixture Risk Assessment for Neurodevelopmental Toxicity Associated with Polybrominated Diphenyl Ethers Used as Flame Retardants. Andreas Kortenkamp, Brunel University London, Department of Life Sciences, College of Health and Life Sciences, United Kingdom.

SYM11: Immunotoxicity Associated with Exposure to Nanomaterials

Room 312

Chairperson(s): Carolyn Vickers, World Health Organization; and Henk van Loveren, Maastricht University.

Due to their properties, nanomaterials have a propensity to interact with components of the immune system. In addition to direct effects on the immune system, interaction with the immune system may be relevant in the facilitation of cancer. The World Health Organization in 2018 released a new Environmental Health Criteria Document, titled Principles and methods for assessing the risk of immunotoxicity associated with exposure to nanomaterials. The symposium will present the WHO document, and review information on the mechanisms of immunotoxicity due to exposure to nanomaterials. Information on carbon nanotubes in a range of products will be provided as examples.

WHO Principles and Methods for Assessing the Risk of Immunotoxicity Associated with Exposure to Nanomaterials. Henk Van Loveren, Maastricht University, The Netherlands.

Occurrence of TiO2 in Food, Supplements and Toothpaste, Resulting Exposure and Toxicokinetics. Minne Heringa, Centre for Safety of Substances and Products (VSP), The Netherlands.

Mechanisms and Consequences of Immune Interactions of Graphene-Based Materials. Bengt Fadeel, Karolinska Institutet, Sweden.

Immunotoxicity and Susceptibility Issues following Pulmonary Exposure to Carbon Nanotubes. James Bonner, North Carolina State University, The United States of America.

SYM12: The Carcinogenicity of Hexavalent Chromium: A Global Public and Environmental Health Concern

Room 315

Chairperson(s): John Pierce Wise Sr., University of Louisville; and Kazuya Kondo, Tokushima University.

Hexavalent chromium [Cr(VI)] is a global environmental pollutant and a major public health concern. It is an established human lung carcinogen, particularly after inhalation exposure, and lung cancer remains the leading cause of cancer death around the world. It is clear that, while cigarette smoking is the most familiar cause of lung cancer, other agents cause a significant amount of the disease. For example, in the United States, of those diagnosed with lung cancer, 1 in 5 women and 1 in 12 men will never have smoked. Thus, understanding how agents other than cigarettes cause lung cancer is a significant need and a key aspect to combating the disease. While Cr(VI) has been known to cause lung cancer for decades, its carcinogenic mechanisms are still poorly understood. Impacts on DNA repair, chromosome structure and number, cellular metabolism, inflammation, apoptosis, cell signaling, centrosome amplification, among others have all been implicated in its carcinogenicity along with epigenetic, mutagenic and aneugenic changes. This symposium will present current perspectives that provide deeper understanding of Cr(VI) carcinogenesis and directions towards solutions with presentations spanning a spectrum of ideas ranging from clinical to laboratory to risk assessment-based paradigms in order to better understand this important carcinogen.

Genetic and Epigenetic Alterations of Lung Cancer in Workers with Chromate Exposure. Kazuya Kondo, Tokushima University, Japan.

Inflammation-Driven Cancer Stem Cells Formation as Promoter of Hexavalent Chromium Carcinogenesis. Carmen Alpoim, University of Coimbra, Portugal.

Mechanisms of Hexavalent Chromium-Induced Genomic Instability: How a Lung Carcinogen Breaks DNA and Inhibits Repair. John Pierce Wise Sr., University of Louisville, The United States of America.

Using the Latest Science in Cancer Risk Assessment for Hexavalent Chromium: Is It Time to Step Away from the Default Regulatory Approaches? Deborah Proctor, ToxStrategies, Inc., The United States of America.

2:30 PM–4:30 PM

SYM13: Acute, Chronic, and Long-Term Pesticide Effects: Mechanisms of Actions, Epidemiological Data, Priority Areas for Research

Room 313

Chairperson(s): Aristidis Tsatsakis, University Crete; and Emanuela Corsini, University of Milano.

Pesticides have been, wrongly or reasonably, associated with increased prevalence of several pathological conditions. Among these, behaviour, dementia and Parkinson’s disease, and cancer, represent particularly relevant public health issues and specific group of pesticide, in particular organ chlorinated compounds, are considered as high concern group. Acute pesticide poisoning still remain an outstanding issue, but data collection, evaluation and interpretation is quite difficult due to a significant underreporting. This workshop aims at critically evaluating the existing evidence on these issues and at identifying priority areas and approaches for research. Each speaker will develop a systematic review on the assigned topic, will show the results and will highlight evidence and doubts. A 15-minute slot at the end of the symposium will be addressed at the discussion of the presentations. The Authors have committed themselves to prepare a paper on these topics, to be published in an international journal.

Pesticide Exposure, Human Behavior, Parkinson’s Disease and Dementia: Evidences, Uncertainties, Open Points. Claudio Colosio, Department of Health Sciences of the University of Milano and International Centre for Rural Health of the San Paolo Hospital of Milano, Italy.

Pesticides and Cancer: Current Knowledge and Epidemiological Evidence. Martin Wilks, Swiss Centre for Applied Human Toxicology, Switzerland.

Challenges in Monitoring and Biomonitoring of Pesticides. Aristidis Tsatsakis, University Crete, Greece.

Acute Pesticide Poisoning and the Effect of Pesticide Regulation. Won Jin Lee, Korea University College of Medicine, The Republic of Korea.

SYM14: Collaborative Approaches to Proactively Advance 3Rs in Nonclinical Drug Development

Room 312

Chairperson(s): Thomas Monticello, Amgen; and Ian Pyrah, Seattle Genetics.

Animal toxicology studies are conducted during drug development to ensure human safety, identify potential organs of toxicity and aid in establishing a clinical starting dose. The conduct of animal toxicology studies is based on historical precedence and regulatory guidance, centered on the assumption that the animal model of choice and the toxicology study provide value in identifying potential human hazards and help ensure patient safety. The 3R approaches are designed to advocate for the replacement of animals with alternative models, the reduction of animal use by improvements in study designs that minimize animal numbers and optimize the information gained per animal, and refinement to minimize distress or harm in situations where the use of animal testing is unavoidable. This session will present proactive considerations of implementing the 3Rs in nonclinical safety assessment that will begin with the overview of the current state of the predictive value of animal studies, including safety pharmacology studies. Opportunities to optimize study designs to incorporate other regulatory mandated endpoints, considerations in species selection and inclusion of recovery animals, approaches to an ‘animal free’ drug development, and finally, opportunities to replace animal testing by implementing microphysiological system technologies (aka ‘organ on a chip’), will also be presented.

Setting the Bar for Positive and Negative Animal Predictive Values: The IQ Translational Database. Thomas Monticello, Amgen, The United States of America.

Applying the 3Rs within Regulatory Toxicology Studies in Drug Development. Helen Prior, National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), United Kingdom.

Animal-Free INDs and CTAs: A Reality or Dream? Michael W. Leach, Pfizer, The United States of America.

Strategic Application of Microphysiological Systems in Safety Assessment to Decrease Dependence on Animal Studies. Brian Berridge, National Toxicology Program, National Institute of Environmental Health Sciences, The United States of America.

SYM15: Empowering Toxicology and Environmental Health Research to Address Disasters and Emerging Threats

Room 315

Chairperson(s): Scott Masten, National Institute of Environmental Health Sciences; and Shoji F. Nakayama, National Institute for Environmental Studies.

Disasters including the World Trade Center attack, Great Eastern Japan Earthquake, Gulf Oil Spill, and recent tropical storms, wildfires and volcanic eruptions have revealed the dire need for improved ability to perform rapid data collection and research to address health-related concerns. The collection of human exposure and health data in the immediate aftermath of public health emergencies and disasters is essential for ensuring situational awareness, shaping the public health response, identifying health research needs, supporting recovery efforts and enhancing future preparedness. Yet the initiation of public health research and response is often delayed by a host of long-standing logistical, process, and regulatory barriers. This session will provide an overview of the critical importance and need for timely toxicology and environmental health research in response to disasters. Speakers will discuss challenges in understanding human health implications and addressing public concerns for recent disasters, highlight research responses to specific large-scale disasters and describe evolving programs to develop improved disaster research response capacity. The session will encourage discussion of the challenges and potential strategies that will enable the conduct of time-critical human health assessments to support decision-making.

Addressing Toxicology and Human Health Concerns with the NIH Disaster Research Response (DR2) Program. Linda Birnbaum, National Institute of Environmental Health Sciences (NIEHS) and National Toxicology Program, The United States of America.

Disaster Response Research Development in Japan. Shoji F. Nakayama, National Institute for Environmental Studies, Japan.

When Disaster Strikes: Response, Research, and Recovery. Ivan Rusyn, Texas A&M University, The United States of America.

Addressing Public Health Hazards Arising from Recent Threats and Disasters in California. Lauren Zeise, Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, The United States of America.

SYM16: Out of the Box: Contribution of the Immune System to Organ Toxicity

Room 316

Chairperson(s): Emanuela Corsini, Università degli Studi di Milano, Milan, Lombardy, Italy; and Nurşen Başaran, Hacettepe University.

Inflammation is known to play a prominent role in several human diseases and is a common response to many stressors, including chemicals. Under normal conditions, inflammation is an adaptive process that contrast infections and is involved in tissue damage repair. However, chemicals can elicit prolonged, severe, and inappropriate inflammatory responses that play a central role in a variety of target organ toxicities. The purpose of this symposium is to link immunotoxicity to target organ toxicity, showing the Janus face of the inflammatory reaction and of the immune system.

Early-Life Exposure to Immunotoxic Compounds and Later-in-Life Diseases. Rodney Reynolds Dietert, Cornell University, The United States of America.

Role of the Immune System in Drug-Induced Liver Injury. Tsuyoshi Yokoi, Nagoya University Graduate School of Medicine, Japan.

Role of Inflammation in Chemical-Induced Kidney Damage. David J. Nikolic Paterson, Department of Nephrology, Australia.

Particles, Fibres, and Lung Toxicity: Effects Beyond the Lung. Flemming R. Cassee, Institute for Risk Assessment Sciences, Utrecht University, The Netherlands.

Thursday, July 18, 2019

2:30 PM–4:30 PM

SYM17: Applying the Key Characteristics Paradigm in Hazard Identification and Risk Assessment

Room 313

Chairperson(s): Martyn Smith, University of California at Berkeley; and Kathryn Guyton, Monographs Programme, International Agency for Research on Cancer, World Health Organization.

This symposium will highlight the potential application of the key characteristics paradigm to the identification of human carcinogens and other health risks from chemical exposures and to suggest consensus solutions and new approaches. Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics, one or more of which are commonly exhibited by established human carcinogens. The key characteristics are distinct from the hallmarks of cancer, which are the properties of tumors. The key characteristics instead reflect the properties of a cancer-causing agent, such as ‘is genotoxic’, ‘is immunosuppressive’ or ‘modulates receptor-mediated effects’. In the cancer hazard identification process, the key characteristics have been used to guide a systematic literature search focused on relevant end points. Further, the National Academy of Sciences recently suggested development of key characteristics for other hazards, such as cardiovascular and reproductive toxicity. The presentations will first describe the scientific basis of key characteristics of carcinogens, discuss how biomarkers of the key characteristics and new assays for their measurement could be applied to assess human cancer risk in drug development, and describe solutions based on the key characteristics to advance cancer research and hazard identification as being applied in national and international settings.

The Key Characteristics of Carcinogens. Martyn T. Smith, University of California at Berkeley, The United States of America.

Applying the Key Characteristics of Carcinogens to Assess Human Cancer Risk in Drug Development. Mark Fielden, Amgen Inc, Comparative Biology and Safety Sciences, The United States of America.

Air Pollution Exhibits Multiple Key Characteristics of Carcinogens. Hideko Sone, Yokohama University of Pharmacy, National Institute for Environmental Studies, Japan.

Application of the Key Characteristics in the IARC Monographs Programme. Kathryn Guyton, Monographs Programme, International Agency for Research on Cancer, World Health Organization, France.

SYM18: Biomarker Qualification: Accelerating Drug Development by Enabling the Use of Novel Diagnostic and Safety Biomarkers

Room 312

Chairperson(s): Jiri Aubrecht, Takeda; and John-Michael Sauer, Critical Path Institute.

The application of novel biomarkers in drug development is needed to accelerate the approval of new therapeutic modalities and improve diagnosis of diseases in clinical practice.  However, the development and qualification of biomarkers is a costly and time-consuming process. Therefore, new innovative scientific approaches and analytical technologies, as well as access to appropriate human samples for biomarker qualification and assay validation, are required. Recently consortia including Critical Path Institute, the Predicative Safety Testing Consortium (PSTC), Innovative Medicines Initiative Safer and Faster Evidence Based Translation Consortium (IMI SAFE-T), International Life Sciences Institute Health and Environmental Sciences Institute (ILSI HESI), and Foundations for the National Institutes of Health Biomarker Consortium (FNIH BC), have identified several promising advances to support biomarker development including scientific advances in analysis and quantification of circulating microRNA and toxicogenomics. In addition, the recent progress in defining the scientific and regulatory expectations for biomarker qualification, led by C-Path and FNIH BC, provides a blueprint for the conduct of regulatory qualification of biomarkers. This symposium will provide insights into innovative approaches and state-of-the-art science involved in the development and world-wide regulatory acceptance of biomarkers for use in drug development, environmental risk assessment, and diagnosis of disease.

How Much Evidence Is Enough to Accept a Biomarker for Regulatory Decision-Making?  Development of Evidentiary Considerations. John-Michael Sauer, Critical Path Institute, The United States of America.

GLDH as an Example of Regulatory Biomarker Qualification: A Liver-Specific Biomarker of Liver Injury in Drug Development and Medical Care. Jiri Aubrecht, Takeda, The United States of America.

Case Studies on Integration of Toxicogenomic Biomarkers in Genetic Toxicology Assessment. Carole Yauk, Health Canada, Environmental Health Centre, Canada.

Serum MicroRNA Signatures as “Liquid Biopsies” for Interrogating Hepatotoxic Mechanisms and Liver Pathogenesis in Human. Julian Krauskopf, University of Maastricht, The Netherlands.

SYM19: Leveraging Zebrafish to Support Global Toxicology Challenges

Room 316

Chairperson(s): Jennifer Freeman, School of Health Sciences, Purdue University; and David Volz, Department of Environmental Sciences, University of California, Riverside.

Over the past 20 years, adoption and integration of the application of zebrafish as a toxicological model system has magnified in most areas of toxicology-based research. As a well-recognized biomedical research model, zebrafish presents numerous strengths that have been leveraged in many toxicity studies. Rapid ex vivo development of a small, near-transparent singular embryo permits ease for assessing chemical perturbations at all stages of early development as well as use in high-throughput chemical screens and automated phenotyping. In addition, a complete genome sequence, array of tools for manipulating gene function, and availability of several thousand mutant and transgenic lines provides, similar to mouse models, readily available resources for comprehensive mechanistic studies of toxicity. Furthermore, maturation at three months of age and a shorter lifespan allow for multi- and transgenerational studies and efficient identification and evaluation of developmental origins of health and disease. As researchers continue to expand the use of the zebrafish in toxicology, limitations of this animal model are also being identified. In this session, speakers will highlight what has been learned from over two decades of using zebrafish as a model for toxicology, spanning mechanistic studies to current applications in high-throughput screening of chemicals and chemical mixtures.

Transcriptomics Coupled with High-Throughput Phenotypic Screening to Accelerate Discovery of Toxicity Pathways. Robert Tanguay, Department of Environmental and Molecular Toxicology, Oregon State University, The United States of America.

Methylmercury-Induced Epigenetic Transgenerational Inheritance of Abnormal Neurobehavior Is Correlated with Sperm Epimutations in Zebrafish. Michael Carvan, School of Freshwater Sciences, University of Wisconsin-Milwaukee, The United States of America.

Lessons Learned on the Toxicokinetics upon Waterborne Chemical Exposure in Zebrafish Larvae. Krishna Tulasi Kirla, Department of Forensic Pharmacology and Toxicology, Eawag, Switzerland.

The Fish Embryo Model: Update and Challenges for Its Potential Regulatory Applications. Marc Léonard, L’OREAL Research and Innovation, Environmental Research Department, France.

SYM20: Recent Trends in Research on Arsenic Toxicity

Room 315

Chairperson(s): Yoshito Kumagai, University of Tsukuba; and Jin-Ho Chung, Seoul National University, Gwanak-gu.

Arsenic is ubiquitously distributed in nature throughout Earth’s crust is also reported to modulate a variety of cellular signal transduction pathways. Speakers in the symposium will introduce recent findings found by each laboratory on the basis of molecular biology or chemical biology. For example, Prof. Zhang introduces disruption of formation of the STX17-SNAP29-VAMP8 SNARE complex, leading to inhibition of the autophagy pathway. Prof. Pi introduces importance of Nrf2/1 in β-cells and adipocytes and provide insight into the effects of inorganic arsenic exposure on insulin secretion and action. Prof. Kumagai introduces (E)-2-alkenals with an α,β-unsaturated aldehyde moiety, which is a common substituent in phytochemicals isolated from C. sativum leaves, activate the Keap1/Nrf2 pathway associated with cellular protection against arsenic. Prof. Chung introduces prometastastic effects of arsenic exposure can indeed contribute to cancer-related mortality.

Arsenic in Oxidative Stress vs. Proteotoxic Stress. Donna Zhang, University of Arizona, The United States of America.

Paradoxical Roles of CNC-bZIP Proteins NRF2 and NRF1 in Arsenic-Induced Dysfunction in Pancreatic β-Cells and Adipocytes. Jingbo Pi, China Medical University, China.

Activation of Nrf2 through Covalent Modification of Keap1 by 2-alkenal Group of Aliphatic Electrophiles in Coriandrum sativum L. Diminishes Arsenic-Mediated Cytotoxicity. Yoshito Kumagai, University of Tsukuba, Japan.

Arsenic May Act As a Pro-Metastatic Carcinogen through Promoting Tumor Cell-Platelet Aggregation. Jin-Ho Chung, Seoul National University, The Republic of Korea.

Trainee Sessions

Tuesday, July 16, 2019

11:30 AM–1:20 PM

Soft Skills Workshop: A Key Differentiator in the Workplace

Separate registration required for limited participants. Box Lunch provided.

Room 312

Chairperson(s): Brinda Mahadevan, Abbot Laboratories; and Patrick Allard, University of California Los Angeles.

This session will focus on few essential must have soft skills such as Listening, Accountability and Taking Initiative, Creative thinking, Emotional awareness and Empathy. An introduction to the soft skills that will speak to personal branding will be presented by the Chairs of the session. This will be followed by three speakers who will illuminate through personal experience/testimonials on how the furnishing of the soft skills is important for smooth communication and key differentiator in the workplace leading to success. There will be a panel discussion and a Q&A session at the end as a conclusion to the workshop.

Wednesday, July 17, 2019

11:00 AM–12:30 PM

Perspectives of Women in Toxicology: Promoting Career Development and Enhancing the Status of Women Toxicologists Around the World

Room 312

Chairperson(s): Tao Wang, Coherus BioSciences; and Nurşen Başaran, Hacettepe University.

Panelists: Nurşen Başaran, Hacettepe University; Betzabet Quintanilla-Vega, CINVESTAV IPN; Hanan Ghantous, US Food and Drug Administration; Mary Gulumian, University of Witwatersrand; Brinda Mahadevan, Abbott Healthcare Pvt; and Tao Wang, Achaogen, Inc.

Although the global share of women in research has increased in the last several decades, women remain underrepresented in many areas of science including toxicology. This is the case not only in developing countries but also in many developed nations. The panel speakers will share the status of women scientists in the field of toxicology in different regions around the globe; describe the challenges faced and opportunities undertaken for career advancement; and highlight successful stories on enhancing recognition of women toxicologists. In addition, available resources for women toxicologists to advance in the field of toxicology will be shared. The panel is aimed to increase awareness of the successes and advances of women in the field of toxicology and impart their experiences on how to further enhance the status of women toxicologists in the different societies.

12:30 PM–1:20 PM

Find Your Mentor

Separate registration required for limited participants.

Room 317A

Chairperson(s): Brinda Mahadevan, Abbot Laboratories; and Patrick Allard, University of California Los Angeles.

This activity seeks to provide attendees with the chance to secure a virtual mentor. Understanding that a large number of participants reside in areas other than continental US, it is critical that this venue serves as a conduit to connect individuals of different countries with mentors who could guide and advise in multiple areas of their professional/personal development.

Platform Presentations

Thursday, July 18, 2019

Presenting author is italic.

9:30 AM–11:00 AM

PL01: Alternatives to Animal Testing

Room 312

California Cruelty-Free Cosmetics Act Establishes First Law in North America That Bans the Sale of Animal-Tested Cosmetics and Ingredients. Elizabeth Baker, Kristie Sullivan. Physicians Committee for Responsible Medicine, Washington, DC, The United States of America.

Practical Implementation of New Approach Methodologies (NAMs): A Corporate Perspective for Diverse Toxicology Applications. Lawrence Milchak, David Brandwein, Colin Owens. 3M, St. Paul, MN, The United States of America.

Hepatocyte-Like Cells Derived from Human Induced Pluripotent Cells Using Small Molecules: Implications of a Transcriptomic Study. Xiugong Gao, Jeffrey Yourick, Robert Sprando. US FDA/CFSAN, Laurel, MD, The United States of America.

High-Throughput Transcriptomics Using Hepatocyte Spheroids to Identify Chemical-Induced Biological-Response Pathways and Associated Toxicity. Sreenivasa Ramaiahgari1, Scott Auerbach1, Trey Saddler1, Nisha Sipes1, Michael DeVito1, Pierre Bushel2, Alex Merrick1, Paules Richard1, Stephen Ferguson1. 1NIEHS/NTP, Durham, NC, The United States of America 2NIEHS, Durham, NC, The United States of America.

The Cross-Laboratory Testing and Evaluation of Two Liver Microphysiological Systems. Courtney Sakolish1, Yizhong Liu1, Celeste Reese2, Richard DeBiasio2, Felipe Lee-Montiel3, Caleb Lee3, Lawrence Vernetti2, Lansing Taylor2, Kevin Healy3, Ivan Rusyn1. 1Texas A&M University, College Station, TX, The United States of America 2University of Pittsburgh, Pittsburgh, PA, The United States of America 3University of California Berkeley, Berkeley, CA, The United States of America.

In Vitro Model for the Prediction of Respiratory Sensitization. Aline Chary1,2, Charlotte Stoffels1, Tommaso Serchi1, Sébastien Cambier1, Elisa Moschini1, Servane Contal1, Jennifer Hennen2, Janine Ezendam3, Brunhilde Blömeke2, Arno Gutleb1. 1Luxembourg Institute of Science and Technology, Belvaux, Luxembourg 2University Trier, Trier, Germany 3Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

PL02: Immunotoxicology

Room 315

Aryl Hydrocarbon Receptor (AhR) Signaling Regulates the Inflammatory Potential of Dendritic Epidermal T Cells. Katja Merches, Charlotte Esser, Kathrin Hochrath, Nadine Teichweyde. IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.

Cadmium Telluride Quantum Dots Exposure Causes Functional Impairments in Monocyte-Derived Dendritic Cells and Alters CD4+ T Cells Differentiation. Tingting Wei, Tianshu Wu, Meng Tang. Southeast University, Nanjing, Jiangsu, China.

Docosahexaenoic Acid as a Prophylactic Treatment for Chronic Particle-Exposed Balb/c Mice. Paige Fletcher1, Ray Hamilton1, James Pestka2, Andrij Holian1. 1University of Montana, Missoula, MT, The United States of America 2Michigan State University, East Lansing, MI, The United States of America.

Lung Function and Immune Effects in Resident Lung Macrophages following Prenatal Exposure to Sodium Arsenite. Kristal Rychlik, Emily Illingworth, Sarah Attreed, Han Zhang, Jeffrey Loube, Wayne Mitzner, Fenna Sillé. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, The United States of America.

Protective Effect of Resveratrol on the Integrity of Alveolar and Intestinal Epithelial Barrier in Staphylococcal Enterotoxin B–Induced Acute Lung Injury. Hasan Alghetaa, Amira Mohammed, Mitzi Nagarkatti, Prakash Nagarkatti. University of South Carolina School of Medicine, Columbia, SC, The United States of America.

Comprehensive Analysis for Immunological Characteristics of Patients with Malignant Mesothelioma and Diffuse Pleural Thickening. Yasumitsu Nishimura1, Suni Lee1, Naoko Kumagai-Takei1, Hidenori Matsuzaki2, Kei Yoshitome1, Kenzo Okamoto3, Takumi Kishimoto4, Takemi Otsuki1. 1Kawasaki Medical School, Kurashiki, Japan 2Prefectural University of Hiroshima, Shobara, Japan 3Hokkaido Chuo Rosai Hospital, Iwamizawa, Japan 4Okayama Rosai Hospital, Okayama, Japan.

PL03: Metals

Room 316

The Sex-Specific Effects of Arsenic on Immune Function, Infectious Disease Risk, and Vaccine Outcomes. Fenna Sillé, Sarah Attreed, Kristal Rychlik, Emily Illingworth, Chloe Kashiwagi, Ashley Fink, Han Zhang, Ian Sanchez, Tyrone Howard, Christopher Heaney, Sabra Klein. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, The United States of America.

Developmental Exposure to Manganese Causes Cognitive Deficits in Rats: Protective Effect of Nutrient Metal Mixture Supplementation. Chand Basha Davuljigari, Srinivasulu Reddy, Rajarami Reddy. Sri Venkateswara University, Tirupati, Andhra Pradesh, India.

The Emerging Dark Side of Nuclear Factor Erythroid 2-related Factor 2 in Chemical Carcinogenesis: Taking Arsenic as an Example. Ruirui Wu1, Ru Sun1, Xiafang Wu1, Huihui Wang1, Jingqi Fu1, Jingbo Pi2, Yuanyuan Xu1. 1China Medical University, Shenyang, Liaoning, China 2China Medical University School of Public Health, Shenyang, Liaoning, China.

Heavy Metal Contamination of Drinking Water Sources and Hepato-renal Toxicities among Residents of a Crude Oil–Contaminated Area in Bayelsa State, Nigeria. Chinyere Usoro1, Caroline Thomas2, Augusta Nsonwu-Anyanwu1. 1University of Calabar, Calabar, Cross River, Nigeria 2Federal Medical Centre, Yenogoa, Bayelsa State, Nigeria.

Determination of Lead (Pb) Exposure on Infants Living around Pb Mining Area in Kabwe, Zambia. Haruya Toyomaki1, John Yabe2, Shouta Nakayama1, Yared Yohannes1,3, Kaampwe Muzandu2, Hazuki Mizukawa4, Yoshinori Ikenaka1,5, Hokuto Nakata1, Takeshi Kuritani6, Mitsuhiro Nakagawa6, Mayumi Ishizuka1. 1Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan 2The University of Zambia, Lusaka, Central, Zambia 3College of Natural and Computational Science, University of Gondar, Gondar, Begemder, Ethiopia 4Graduate School of Agriculture, Ehime University, Matsuyama, Ehime, Japan 5School of Environmental Sciences and Development, North-West University South Africa, Potchefstroom, North West, South Africa 6Graduate School of Science, Hokkaido University, Sapporo, Hokkaido, Japan.

Prenatal Exposure to Toxic Metals Modulates Global and Specific DNA Methylation and Expression of Repair Genes. Nereida Montes-Castro1, Isabel Alvarado-Cruz1, Luisa Torres-Sánchez2, Israel García-Aguiar1, Angel Barrera-Hernández1, Consuelo Escamilla-Núñez2, Luz Maria Del Razo-Jiménez 1, Betzabet Quintanilla Vega1. 1Center for Research and Advanced Studies (Cinvestav), Mexico City, Mexico 2National Institute of Public Health, Cuernavaca, Morelos, Mexico.

PL04: Risk and Safety Evaluation

Room 313

Evaluating Mechanistic Data in Hazard Assessment: Integration of Key Characteristics and Mode of Action. Bette Meek. University of Ottawa, Ottawa, Ontario, Canada.

A New Method to Evaluate Toxicological Data Reliability in Food Safety Risk Assessments. Qian Bian1, Ping Yu1, Jun Wu1, Zhongming Lyn1, Yan Song2, Lei Zhang2, Zhaoping Liu2. 1Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 2China National Center for Food Safety Risk Assessment, Beijing, China.

Development of New Risk Assessment Guideline of Food Contact Materials Based on the TTC Concept in Food Safety Commission of Japan. Atsushi Ono1, Masahiro Nakamoto2, Naofumi Iizuka2, Makiko Isozaki2. 1Okayama University, Okayama, Japan 2Food Safety Commission of Japan, Tokyo, Japan.

Establishment of a Reference Chemical Database to Evaluate In Vitro and In Silico Approaches to Assess Respiratory Sensitization to Facilitate Development of IATA. Kristie Sullivan1, Nancy Baker2, Stella Cochrane3, Steven Enoch4, Janine Ezendam5, Grace Patlewicz6, Ramya Rajagopal3, Erwin Roggen7, Raja Settivari8, Katherina Sewald9. 1Physicians Committee for Responsible Medicine, Washington, DC, The United States of America 2Leidos, Research Triangle Park, NC, The United States of America 3Unilever Safety and Environmental Assurance Centre, Bedford, United Kingdom 4Liverpool John Moores University, Liverpool, United Kingdom 5RIVM, Bilthoven, The Netherlands 6US EPA/NCCT, Research Triangle Park, NC, The United States of America 73RsMC ApS, Lyngby, Denmark 8Corteva Agriscience, Newark, DE, The United States of America 9Fraunhofer ITEM, Hannover, Germany.

The Research of Health Risk Factors in the Field of Occupational Health and Environmental Toxicology in Laboratory Workplaces. Nalinee Sripaung, Areepit Promrat, Satit Namwicha. Bureau of Occupational and Environmental Diseases, Department of Disease Control, Ministry of Public Health, Muang District, Nonthaburi, Thailand.

Do the REACH Derived No-Effect Levels Extend the Landscape of Occupational Exposure Guidance Values? Linda Schenk1,2, Gunnar Johanson1. 1Karolinska Institutet, Stockholm, Sweden 2KTH - Royal Institute of Technology, Stockholm, Sweden.

11:00 AM–12:30 PM

PL05: Computational Toxicology

Room 315

How to Choose the Right Cancer Cell Line for Your Research: A Transcriptomes-Guided Approach. Xin Shao, Yang Hu, Jie Liao, Xuechun Chen, Yunru Yu, Lingqi Yu, Xiaoyan Lu, Ni Ai, Yi Wang, Xiaohui Fan. Zhejiang University College of Pharmaceutical Sciences, Hangzhou, Zhejiang, China.

Fit-for-Purpose Use of High-Throughput Toxicokinetics for Predicting Potential Human Health Risk. Nisha Sipes. NIEHS, Research Triangle Park, NC, The United States of America.

In Vivo Toxicity Prediction Modeling with Tox21 Data to Aid Regulatory Sciences. Ruili Huang. NIH/NCATS, Rockville, MD, The United States of America.

A Case Study in Quantitative Generalized Read-Across (GenRA) Predictions Using Acute Oral Toxicity. George Helman1,2, Imran Shah2, Grace Patlewicz2. 1Oak Ridge Institute for Science and Education, Oak Ridge, TN, The United States of America 2US EPA/NCCT, Research Triangle Park, NC, The United States of America.

Using (Q)SAR Models to Inform Drug Safety Assessment. Naomi Kruhlak, Marlene Kim, Christopher Ellis, Lidiya Stavitskaya. US FDA/CDER, Silver Spring, MD, The United States of America.

Reproducibility of Computational Toxicology: The Prerequisite for Regulatory Applications. Huixiao Hong. US FDA/NCTR, Jefferson, AR, The United States of America.

PL06: Nanotoxicology

Room 312

Neurological Risks of Inhaled Incidental Particulates and Engineered Nanomaterials. Krishnan Sriram, Amy Jefferson, Gary Lin, Samuel Stone, Aliakbar Afshari, Walter McKinney, James Antonini, Michael Wolfarth, Dale Porter. NIOSH, Morgantown, WV, The United States of America.

Mitochondrial Respiration and Metal Bioaccumulation in Zebrafish Developmental Stages (Danio rerio) Evaluating Three Functionalized Groups of CdTe Quantum Dot Nanoparticles. Suanne Bosch, Tarryn Botha, Victor Wepener. Water Research Group, Potchefstroom, South Africa.

Development of Physiologically Relevant In Vitro Models for Assessment of Nanoparticle-Induced Physicochemical Property–Dependent Cytotoxicity of Human Lung Cells. Liying Rojanasakul1, Raymond Derk1, Jhy-Charm Soo1, Philip Demokritou2, Dilpreet Singh2, Tiffany Kornberg1,3, Todd Stueckle1, Yon Rojanasakul3, Jayme Coyle1. 1NIOSH, Morgantown, WV, The United States of America 2Harvard University, Boston, MA, The United States of America 3West Virginia University, Morgantown, WV, The United States of America.

Nano ZnO Exposure Alters In Vitro Lipidomic Profiles of Human Immune Cells. Mala Jayamanne1, Paul Wright2, Terence Turney3, Philip Marriott1. 1Monash University, Clayton, Melbourne, Victoria, Australia 2RMIT University, Bundoora, Melbourne, Victoria, Australia 3Monash University, Clayton, Melbourne, Victoria, Australia.

Silver Nanoparticles Promote Procoagulant Activity of Red Blood Cells: A Potential Risk of Thrombosis in Susceptible Population. Yiying Bian, Jin-Ho Chung, Byung Hoon Lee. Seoul National University, Seoul, The Republic of Korea.

CdTe Quantum Dots Increase Microglial Polarization in Mice and Trigger Damage to Hippocampal Neurons. Keyu He, Tianshu Wu, Meng Tang. Southeast University, Nanjing, Jiangsu, China.

PL07: Neurotoxicology

Room 316

K-variant BCHE and Pesticide Exposure: Interactive Genome and Parkinson’s Disease. Mohamed Mosaad Salama1, Thomas Roesler2, Ali Shalash3, Urlich Müller4, Astrid Dempfle5, Gregor Kuhlenbäumer5, Gunter Hoeglinger2, ENND Consortium1. 1Mansoura University, Mansoura, Egypt 2Technical University of Munich, Munich, Germany 3Ain Shams University, Cairo, Egypt 4Justus Liebig University Giessen, Giessen, Germany 5Kiel University, Kiel, Germany.

THC Treatment Improved Neuronal Functions by Decreasing HIV gp120-Mediated Neurotoxicity. Amira Mohammed, Hasan Alghetaa, Prakash Nagarkatti, Mitzi Nagarkatti. University of South Carolina School of Medicine, Columbia, SC, The United States of America.

Manganese-Mycobacterium tuberculosis Interactions: Central and Peripheral Effects. Nick Filipov, Kaori Sakamoto, Tuhina Gupta, Ryan Mote, Robert Hogan, Davis Reardon. University of Georgia, Athens, GA, The United States of America.

Function of LncRNA NR_030777 in Affecting Cell Proliferation and Apoptosis and Protection of Motor Function by Regulating Zfp326/Cpne5 in Nerve Cell Damage Induced by Paraquat. Hongyu Yang1, Qingxia Lin1, Nengzhou Chen1, Zhousong Luo1, Jing Li1, Fuli Zheng1, Qunwei Zhang2, Siying Wu1, Huangyuan Li1. 1Fujian Medical University, Fuzhou, Fujian, China 2University of Louisville, Louisville, KY, The United States of America.

Effect of Silver Nanoparticles on Neural Differentiation in Human iPS Cells. Yasunari Kanda, Shigeru Yamada. National Institute of Health Sciences, Kawasaki, Kanagawa, Japan.

Effect of MLL Modified H3K4me3 on Aluminum Induced Cognitive Impairment—Both Population and Animal Epigenetic Studies. Qiao Niu. Shanxi Medical University, Taiyuan, Shanxi, China.

PL08: Reproductive and Developmental Toxicology

Room 313

Determination of Epigenetic Modifications in Fetal Brain Exposed to Methylmercury during Development. Hisaka Kurita, Manami Hatano, Suzuna Go, Kana Matsumoto, Masatoshi Inden, Isao Hozumi. Gifu Pharmaceutical University, Gifu, Japan.

Exposure to Low Doses of 3-Methylcholanthrene Impacts on the Oocyte Integrity without Causing Systemic Cytotoxicity. Eric Rhon Calderón, Rocío Galarza, Alicia Faletti. CEFYBO-CONICET, School of Medicine, University of Buenos Aires, CABA, Argentina.

Downregulation of SDF1/CXCR4 Signaling Mediates Ethanol-Induced Craniofacial Anomalies and Cranial Nerve Defects in Zebrafish Embryos by Disrupting Neural Crest Cell–Placode Interaction. Huadong Fan, Fuqiang Yuan, Jie Liu, Shao-yu Chen. University of Louisville Health Sciences Center, Louisville, KY, The United States of America.

Teratogen Assay Using Gene Expression Profiles of Developmental Regulators in Morphogenetic Aggregates of Human Embryonic Stem Cells. Yusuke Marikawa, Hong-Ru Chen, Vernadeth Alarcon. University of Hawaii John A. Burns School of Medicine, Honolulu, HI, The United States of America.

3- to 7-Ring Polycyclic Aromatic Hydrocarbons Are the Main Inducers of the In Vitro Prenatal Developmental Toxicity Observed with Some Petroleum Substances. Lenny Kamelia1, Laura de Haan1, Hans Ketelslegers2, Ivonne Rietjens1, Peter Boogaard1,3. 1Wageningen University and Research, Wageningen, Gelderland, The Netherlands 2European Petroleum Refiners Association, Brussels, Belgium 3Shell International BV, The Hague, The Netherlands.

Gestational and Lactational Exposure to the Di(2-Ethylhexyl) Phthalate (DEHP) Increases Mammary Gland Weight in Adult Female Rats Potentially by the Peroxisome Proliferator-Activated Receptor (PPAR) Pathway Activation. Bélinda Crobeddu1, Elise Kolasa1, Bernard Robaire2, Isabelle Plante1. 1INRS - Institut Armand-Frappier, Laval, Quebec, Canada 2McGill University, Montréal, Quebec, Canada.

IUPHAR IUTOX Exchange Session

Thursday, July 18, 2019

12:30 PM–2:30 PM

Precision Medicine and ADME-Targets

Room 312

Chairperson(s): Andrew Somogyi, University of Adelaide; and Nuala Helsby, University of Auckland.

ADME targets have been a major example through which Precision Medicine has been shown to be clinically important and useful, with resultant Guidelines development and promotion. Although much has been based on classical pharmacogenetic investigations, new directions into epigenetic factors are slowly evolving with mixed results for clinical relevance. In this symposium, speakers will address a) the role of germline ADME variants in providing a greater understanding of the efficacy and life-threatening toxicity to widely-used chemotherapy drugs; b) the role of genetic and epigenetic factors in drug uptake transporters and their potential contribution to Precision Medicine; c) the importance of recognizing that ethnicity can be a major factor through investigations of the pharmacogenetics of the Australian Aborigine and, d) the increasingly recognized concept of reverse translational studies in identifying previously unknown mechanisms of drug-induced toxicity. The audience will gain a greater understanding of how far Precision Medicine has evolved over the past decades and its future with respect to ADME Targets and clinical relevance.

Pharmacogenomics of Chemotherapy: Personalizing Old Drugs. Nuala Helsby, University of Auckland, New Zealand.

New Vistas in Prediction of Nongenetic Variability in UGT2B17 for Applications in Precision Medicine. Bhagwat Prasad, University of Washington, The United States of America.

Precision Medicine for First Nations People: Lessons from Aboriginal Australians. Andrew Somogyi, University of Adelaide, Australia.

Reverse Translational Studies to Identify Novel Mechanisms of Drug-Induced Toxicity. Deanna Kroetz, University of California San Francisco, The United States of America.

Scientific Program

The theme of this meeting, to ensure relevance and interest to the worldwide community of toxicologists and environmental health scientists, is “Toxicology Solutions for Global Public, Environmental, and Personal Health.”

The Scientific Program Committee has worked diligently with IUTOX and other societies to create an inclusive and diverse program that highlights excellence in science and practice of toxicology around the Globe, ensuring the balance of interests of different countries and world regions. Attendees will find that Symposia and Continuing Education courses are informative, inspiring, and present strategies that can be implemented to improve human and environmental health in countries with both robust and developing research and regulatory enterprises. ICTXV will serve as a global forum for the exchange of ideas that can create impacts at all time scales, create lasting partnerships, and lead to measurable elevation of the competency of toxicologists globally.

home_eco_blog5

ICTXV Scientific Program Committee

  • William Slikker Jr. (USA) – ICTXV Chair
  • Ivan Rusyn (USA) – ICTXV Scientific Program Committee Chair
  • Peter N. Di Marco (Australia) – ICTXV Scientific Program Committee Co-Chair and IUTOX President-Elect
  • Peter Goering (USA) – ICTXV Scientific Program Committee Co-Chair and Chair of the Continuing Education Committee
  • Silvia Barros (Brazil)
  • A. Nurşen Başaran (Turkey)
  • Emanuela Corsini (Italy)
  • Claude Emond (Canada)
  • Lijie Fu (China)
  • Mary Gulumian (South Africa)
  • Keon Wook Kang (Republic of Korea)
  • Yoshito Kumagai (Japan)
  • Ofelia Olivero (USA)
  • Betzabet Quintanilla Vega (Mexico)
  • M. Wahajuddin (India)

ICTXV Meeting

Join us in Hawaii 2019


July 15–18, 2019
Hawaii Convention Center
Honolulu, Hawaii, USA

Contact us: +1.703.438.3115
Email: sothq@toxicology.org