Health And Environmental Sciences Institute

THE HEALTH AND ENVIRONMENTAL SCIENCES INSTITUTE (HESI) IS A NONPROFIT INSTITUTION WHOSE MISSION IS TO ENGAGE SCIENTISTS FROM ACADEMIA, GOVERNMENT, INDUSTRY, NONPROFIT, AND OTHER RESEARCH INSTITUTIONS TO IDENTIFY AND RESOLVE GLOBAL HEALTH AND ENVIRONMENTAL ISSUES.

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 2022, THE COMMITTEE CONTINUED TO SPONSOR PROJECTS ADDRESSING CARDIOVASCULAR SAFETY TESTING, PUBLISHED ONE SCIENTIFIC MANUSCRIPT IN A PEER-REVIEWED TECHNICAL JOURNAL BASED ON THE COMMITTEE'S RESEARCH AND PRESENTED 8 TIMES AT PUBLIC SCIENTIFIC MEETINGS. AN ADDITIONAL 5 MANUSCRIPTS ARE IN PROGRESS. KEY PROJECTS INCLUDED INITIATION 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 COLLECTION 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.

IN VITRO GENOTOXICITY; IMMUNOTOXICOLOGY; CT TRACS; PROTEIN ALLERGENICITY; THRIVE; DEV AND REPRODUCTIVE TOX; ECO RISK; ACSA; EMERGING ISSUES CMTE; EI OTOTOX RA; ANNUAL MEETING; PB/PK; PROTAC; COMMUNICATIONS AND OUTREACH; RA 21ST CENTURY; UVCB; GRATC; ENV EPI RA; INNOVATION PRIZE; NEOUROTOX BIOMARKERS; EXTERNAL ADVISORY; FAST FUND; BIOACCUMULATION; ANIMAL ALTERNATIVES IN ERA; PROG STRATEGY AND STEWARDSHIP; HESI HELPS, AND OTHERS.

BOTANICAL SAFETY CONSORTIUM (BSC): THE BSC WAS OFFICIALLY CONVENED IN NOVEMBER 2019, AS THE RESULT OF A MEMORANDUM OF UNDERSTANDING BETWEEN THE US FDA, THE NATIONAL INSTITUTES OF HEALTH'S NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES (NIEHS), AND THE NON-PROFIT HEALTH AND ENVIRONMENTAL SCIENCES INSTITUTE (HESI). THE CONSORTIUM IS SUPPORTED VIA US FEDERAL FUNDING AND PRIVATE SECTOR CONTRIBUTIONS TO CREATE A PARTNERSHIP TO ADVANCE THE SCIENCE OF BOTANICAL EVALUATION. WITH THE ENGAGEMENT OF A BROAD GROUP OF GLOBAL STAKEHOLDERS, THE BSC'S MISSION IS TO ESTABLISH SUITABLE LEVELS OF CHEMICAL CHARACTERIZATION FOR BOTANICALS AND IDENTIFY FIT-FOR-PURPOSE IN VITRO AND IN SILICO ASSAYS THAT CAN BE USED TO EVALUATE BOTANICAL SAFETY. THE BSC IS COMPRISED OF EXPERTS IN AREAS RELATED TO PHARMACOGNOSY, NATURAL PRODUCTS CHEMISTRY, MODELING, TOXICOLOGY, AND/OR NEW APPROACH METHODOLOGIES. AN UP-TO-DATE LIST OF PARTICIPATING ORGANIZATIONS CAN BE FOUND AT WWW.BOTANICALSAFETYCONSORTIUM.ORG. PRIORITIZED TOXICITY ENDPOINTS LED TO THE FORMATION OF SIX ENDPOINT WORKING GROUPS: HEPATOTOXICITY, CARDIOTOXICITY, NEUROTOXICITY, GENOTOXICITY, DEVELOPMENTAL AND REPRODUCTIVE TOXICITY (DART), AND SYSTEMIC TOXICITY. THERE IS ALSO CONSIDERABLE FOCUS ON EVALUATION OF ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION (ADME) AND BOTANICAL-DRUG INTERACTIONS (BDIS) WITHIN THESE WORKING GROUPS. ALL TOXICOLOGICAL ENDPOINT GROUPS WORK IN COLLABORATION WITH THE CHEMICAL AND DATA ANALYSIS GROUPS FOR SUBSTANCE CHARACTERIZATION, EXPERIMENTAL DESIGN, AND ULTIMATELY, EVALUATION OF RESULTS. IN VITRO TO IN VIVO EXTRAPOLATION (IVIVE) IS A KEY CONSIDERATION FOR THE VARIOUS ENDPOINTS AND ASSAYS TO ENSURE THAT THE RESULTS FROM THE ASSAYS CAN BE APPROPRIATELY COMPARED TO AVAILABLE ANIMAL AND HUMAN SAFETY INFORMATION. IN 2022, THE BSC PRESENTED AT VARIOUS SCIENTIFIC MEETINGS INCLUDING THE SOCIETY OF TOXICOLOGY ANNUAL MEETING AND THE INTERNATIONAL CONGRESS OF TOXICOLOGY.

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 RECENTLY FORMED 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 RECENTLY INITIATED 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 TO PERFORM A MULTI-SITE TRIAL FOR QUALIFICATION. THE COMMITTEE HAS TWO MANUSCRIPTS CLOSE TO SUBMISSION AND WILL PRESENT AT TWO SCIENTIFIC MEETINGS IN 2023.