OpenTox 2022 Virtual Conference 

DEVELOPMENT OF A DATA MANAGEMENT RESOURCE TO SUPPORT ANIMAL-FREE  TOXICITY TESTING AND HUMAN RISK ASSESSMENT

A requirement of the European Commission’s Horizon 2020 Research and Innovation funding  program is that the three funded consortia; ONTOX, PrecisionTox, and RISK-HUNT3R;  collaborate on cross-consortia projects. This collaborative group, ASPIS (Animal-free Safety  Assessment of Chemicals: Project Cluster for Implementation of Novel Strategies), consist of  over 70 institutions across 16 European countries and the United States. It utilizes available and  newly generated data to improve the accuracy, speed, and affordability of chemical risk  assessment without the use of laboratory animals. The goals of the three consortia overlap but are  distinct. ONTOX uses a generic strategy to predict systemic repeated dose toxicity effects in  combination with exposure assessment. PrecisionTox applies multi-omics, computational  approaches, and genetic variation to understand fundamental mechanisms of chemicals toxicity,  while reducing traditional animal testing assessment. RISK-HUNT3R is developing, validating,  and implementing integrated approaches to assess chemical exposure, toxicokinetics, and  toxicodynamics for the development of next-generation risk assessment strategies. To support  the efforts of ASPIS, a common database is being developed that will include cheminformatics,  in vivo and in vitro toxicity data, transcriptomic and metabolomic data from multiple species, policy, legal and risk assessment documents, mathematical and theoretical models, and novel  tools to analyze this information. The ASPIS-wide database will contain diverse and evolving  information not typically found in a single database and support users with varied questions. The  creation of this database requires coordinating the input from multiple end-users with diverse  needs, requirements and project goals and database developers with varied skill sets.  Additionally, efforts and timelines of database development teams within each consortium must  be accommodated. A project coordinator has been assigned to facilitate the development of the  ASPIS-wide data management resource. Organizational schemes, challenges, oppertunities, and  sucesses will be presented.

CV: Dr. Freedman received his Ph.D. in Molecular Pharmacology from the Albert Einstein College of  Medicine, Bronx, NY. His academic appointments include AT&T Bell Laboratories, Duke  University, National Institute of Environmental Health Sciences, NIH, University of Louisville,  School of Medicine, and the University of North Carolina at Chapel Hill. His research involves understanding how exposures to environmental toxicants contribute to the development and/or exacerbation of human diseases. Specifically, he is examining the roles of transition metals in the etiology of prostate cancer, metabolic disorders, and Autism Spectrum Disorder. He is applying a systems biological approach; where interactions among phenotypes, genetics, and environmental factors at the molecular, cellular, organ, and whole organism level are characterized in an integrated manner. This approach allows him to develop novel models that delineate the mechanism(s) by which multiple factors come together to produce human disease. By applying classic and reverse-genetic approaches, molecular biology, and modern transcriptomics; regulatory pathways that respond to metals are identified and characterized. He utilizes model organisms (Caenorhabditis elegans and mice) and mammalian cell culture, as well as high throughput screening technologies to explore the environmental contributions to human disease. Another focus of his research is to support international efforts to reduce the number of animals in toxicity testing: the 3Rs. Dr. Freedman has developed C. elegans as a  toxicological model opened He has developed several assays with robust statistical analyses that quantitatively measure the effects of chemical compounds on C. elegans growth, feeding,  reproduction, and locomotion. These assays have been applied to almost 2,000 chemicals.