HEALTH AND ENVIRONMENTAL SCIENCES INSTITUTE

EMERGING SYSTEMS TOXICOLOGY FOR THE ASSESSMENT OF RISK (ESTAR): THE MISSION OF THIS COMMITTEE IS TO DEVELOP AND DELIVER INNOVATIVE SYSTEMS TOXICOLOGY APPROACHES FOR RISK ASSESSMENT. THIS INCLUDES THE CATALYZE ADOPTION OF NEW TRANSLATIONAL AND PREDICTIVE TOOLS THAT GUIDE DECISION-MAKING BASED ON MECHANISTIC UNDERSTANDING OF TOXICOLOGICAL RESPONSE, ENGAGING THE GLOBAL SCIENTIFIC COMMUNITY TO PROMOTE INTERNATIONAL ACCEPTANCE OF GENOMIC BIOMARKERS FOR DECISION-MAKING, AND IDENTIFYING AND CHARACTERIZING BIOFLUID AND TISSUE-BASED GENOMIC BIOMARKERS FOR TOXICOLOGY. THE COMMITTEE HAS SIX ACTIVE PROJECTS, INCLUDING THE OMICS FOR ASSESSING SIGNATURES FOR INTEGRATED SAFETY (OASIS) CONSORTIUM, WHICH IS INVESTIGATING THE USE OF CELL PAINTING AND TRANSCRIPTOMICS FROM IN VITRO MODELS AND COMPARING THEM TO EXISTING RAT IN VIVO DATA. ANOTHER PROJECT IS EVALUATING THE USE OF ERROR CORRECTED SEQUENCING TO DETECT CLONAL EXPANSION INDUCED BY NON-GENOTOXIC CARCINOGENS. EXISTING PROJECTS HAVE MADE GREAT PROGRESS AS WELL IN 2023. THE TGX-DDI PROJECT WAS AWARDED A U01 GRANT FROM THE US FDA'S BIOMARKER QUALIFICATION PROGRAM, WHICH ALLOWED IT TO COMPLETE A MULTI-SITE TRIAL FOR QUALIFICATION. THE COMMITTEE HAS PUBLISHED TWO MANUSCRIPTS THIS YEAR AND HAS PRESENTED AT 4 SCIENTIFIC MEETINGS.

CARDIAC SAFETY TECHNICAL COMMITTEE: THE MISSION OF THE CARDIAC SAFETY TECHNICAL COMMITTEE IS TO IMPROVE PUBLIC HEALTH BY REDUCING UNANTICIPATED CARDIOVASCULAR-RELATED ADVERSE EFFECTS FROM DRUGS OR CHEMICALS AND DEVELOP INNOVATIVE APPROACHES TO SUPPORT EARLY DETECTION AND PREDICTION AS WELL AS IMPROVED UNDERSTANDING OF CARDIOVASCULAR TOXICOLOGY AND PATHOBIOLOGY. IN 2023, THE COMMITTEE CONTINUED TO SPONSOR PROJECTS ADDRESSING CARDIOVASCULAR SAFETY TESTING, PUBLISHED TWO SCIENTIFIC MANUSCRIPTS IN A PEER-REVIEWED TECHNICAL JOURNAL BASED ON THE COMMITTEE'S RESEARCH AND PRESENTED 9 TIMES AT PUBLIC SCIENTIFIC MEETINGS. AN ADDITIONAL 6 MANUSCRIPTS ARE IN PROGRESS. KEY PROJECTS INCLUDED CONTINUATION OF A NEW STUDY TO EXPLORE DRUG-INDUCED BLOOD PRESSURE CHANGES, A STUDY TO IDENTIFY BIOMARKERS OF BLEEDING DISORDERS, PROJECT PLANNING TO EXPLORE CARDIAC FUNCTION AND SODIUM CHANNEL BLOCK, AND COMPLETION OF DATA ANALYSIS FOR A NEW STUDY TO EXPLORE USE OF CARDIAC STEM CELLS TO PREDICT TOXICITY. THE COMMITTEE ALSO CONTINUED THEIR SUPPORT OF TWO GRANTS AWARDED THROUGH FDA AND NIH IN SUPPORT OF A STRATEGIC FRAMEWORK TO ENHANCE THE USE OF MECHANISTIC STUDIES TO PREDICT POTENTIAL CARDIAC RISKS FOR PHARMACEUTICALS. THE GRANTS INCLUDE SUBCONTRACTS AT SEVERAL LABORATORIES IN THE US AND EUROPE.