R01ES036575

ACCUMULATION OF MICRO- AND NANOPLASTIC PARTICLES IN MAMMALIAN TISSUES: A TRANSLATIONAL STUDY - ABSTRACT THE UTILIZATION AND SUBSEQUENT DISPOSAL OF PLASTICS AND PLASTIC BASED PRODUCTS CONTINUES TO RISE EXPONENTIALLY. CURRENT PERVASIVENESS OF MICRO- AND NANOPLASTIC PARTICLES (MNPS) IN THE ENVIRONMENT RESULTS IN SIGNIFICANT EXPOSURE TO HUMAN POPULATIONS VIA INHALATION AND INGESTION. MNP CONTAMINANTS HAVE BEEN DISCOVERED IN THE AIR WE BREATHE, THE FOOD WE EAT, AND IN 81% OF TAP WATER SAMPLES TESTED AROUND THE GLOBE. SAMPLES TAKEN FROM HUMAN SUBJECTS, INCLUDING OUR PRELIMINARY DATA, IDENTIFY MNP DEPOSITION IN TISSUES (E.G., LUNG, HEART, BLOOD, THROMBI, AND PLACENTA) AND EXCRETA (E.G., SEMEN, BREAST MILK, BRONCHOALVEOLAR LAVAGE FLUID, AND FECES). THESE FINDINGS INDICATE THAT NOT ONLY ARE HUMANS EXPOSED TO MNP, BUT THESE PERVASIVE PART ICLES BYPASS PROTECTIVE ANATOMICAL BARRIERS, ACCUMULATING WITHIN SYSTEMIC TISSUES. ANIMAL MODELS REPRODUCE THESE FINDINGS IN A LABORATORY ENVIRONMENT, RESULTING IN MNP ACCUMULATION IN SYSTEMIC TISSUES AND ASSOCIATIONS WITH PATHOLOGIC CHANGES. MNPS HAVE ALSO BEEN IDENTIFIED IN THE PLACENTA AND FETAL ORGANS OF RODENT MODELS AFTER PULMONARY OR GASTRIC EXPOSURE. OUR PRELIMINARY DATA SUGGEST MATERNAL TRANSFER OF MNP TO THE OFFSPRING, WITH MNP DEPOSITION REMAINING IN OFFSPRING TISSUES FOR AT LEAST 2 WEEKS AFTER BIRTH, 16 DAYS AFTER THE LAST MATERNAL EXPOSURE. DESPITE THE EXTENT OF WORLD-WIDE MNP EXPOSURE, THE QUANTIFIED CONCENTRATION OF MNP WITHIN SYSTEMIC TISSUES IS UNKNOWN. ANALYSES HAVE BEEN CONDUCTED USING MICROSCOPIC FIXED TISSUE ANALYSES OR CHEMICAL EXTRACTION- BASED TECHNIQUES. UNFORTUNATELY, THESE METHODOLOGIES CANNOT CURRENTLY BE ADEQUATELY COMPARED. CURRENTLY, THERE IS NO “GOLD STANDARD” METHODOLOGY THAT MEETS ALL REQUIREMENTS FOR IDENTIFYING MNPS IN BIOLOGICAL TISSUES. FURTHERMORE, THE ROLE OF SEX, AGE, AND ETHNICITY IN THE ACCUMULATION OF MNPS IN HUMAN TISSUES HAS NOT YET BEEN EXPLORED. THIS PROJECT WILL INVESTIGATE INTER-TISSUE MNP ACCUMULATION IN RODENT MODELS OF MNP EXPOSURE VIA INTRATRACHEAL INSTALLATION OR GAVAGE, USING OVERLAPPING STATE-OF-THE-ART DETECTION METHODOLOGIES TO QUANTIFY AND CONFIRM MNP DEPOSITION. WE WILL THEN COMPARE THESE CONCENTRATIONS TO THOSE OBTAINED FROM HUMAN AUTOPSY SAMPLES. INNOVATIVE STATISTICAL METHODS FOR INTEGRATING CALIBRATION SAMPLES WITH RESULTS FROM DIFFERENT ANALYTICAL METHODS WILL BE EMPLOYED TO CORRECT FOR MEASURE ERRORS. THESE TRANSLATIONAL STUDIES WILL PROVIDE FURTHER RATIONALE TO RELATE HUMAN AND LABORATORY MNP TRANSLOCATION AND DEPOSITION STUDIES. TO FULLY ASSESS MNP TOXICITIES, WE MUST FIRST UNDERSTAND THE MEASURED MASS DEPOSITION BASED ON KNOWN EXPOSURE DOSES. SUCCESSFUL COMPLETION OF THESE STUDIES WILL PROVIDE THE FOUNDATIONAL PHYSIOLOGICAL DOSES TO ADVISE FUT URE IN VITRO AND EX VIVO MNP TOXICOLOGICAL STUDIES.

New York University

TO FOSTER UNDERSTANDING OF HUMAN HEALTH EFFECTS OF EXPOSURE TO ENVIRONMENTAL AGENTS IN THE HOPE THAT THESE STUDIES WILL LEAD TO: THE IDENTIFICATION OF AGENTS THAT POSE A HAZARD AND THREAT OF DISEASE, DISORDERS AND DEFECTS IN HUMANS, THE DEVELOPMENT OF EFFECTIVE PUBLIC HEALTH OR DISEASE PREVENTION STRATEGIES, THE OVERALL IMPROVEMENT OF HUMAN HEALTH EFFECTS DUE TO ENVIRONMENTAL AGENTS, THE DEVELOPMENT OF PRODUCTS AND TECHNOLOGIES DESIGNED TO BETTER STUDY OR AMELIORATE THE EFFECTS OF ENVIRONMENTAL AGENTS, AND THE SUCCESSFUL TRAINING OF RESEARCH SCIENTISTS IN ALL AREAS OF ENVIRONMENTAL HEALTH RESEARCH. SUPPORTED GRANT PROGRAMS FOCUS ON THE FOLLOWING AREAS: (1) UNDERSTANDING BIOLOGICAL RESPONSES TO ENVIRONMENTAL AGENTS BY DETERMINING HOW CHEMICAL AND PHYSICAL AGENTS CAUSE PATHOLOGICAL CHANGES IN MOLECULES, CELLS, TISSUES, AND ORGANS, AND BECOME MANIFESTED AS RESPIRATORY DISEASE, NEUROLOGICAL, BEHAVIORAL AND DEVELOPMENTAL ABNORMALITIES, CANCER, AND OTHER DISORDERS, (2) DETERMINING THE MECHANISMS OF TOXICITY OF UBIQUITOUS AGENTS LIKE METALS, NATURAL AND SYNTHETIC CHEMICALS, PESTICIDES, AND MATERIALS SUCH AS NANOPARTICLES, AND NATURAL TOXIC SUBSTANCES, AND THEIR EFFECTS OF ON VARIOUS HUMAN ORGAN SYSTEMS, ON METABOLISM, ON THE ENDOCRINE AND IMMUNE SYSTEMS, AND ON OTHER BIOLOGICAL FUNCTIONS, (3) DEVELOPING AND INTEGRATING SCIENTIFIC KNOWLEDGE ABOUT POTENTIALLY TOXIC AND HAZARDOUS CHEMICALS BY CONCENTRATING ON TOXICOLOGICAL RESEARCH, TESTING, TEST DEVELOPMENT, VALIDATION AND RISK ESTIMATION, (4) IDENTIFYING INTERACTIONS BETWEEN ENVIRONMENTAL STRESSORS AND GENETIC SUSCEPTIBILITY AND UNDERSTANDING BIOLOGIC MECHANISMS UNDERLYING THESE INTERACTIONS, INCLUDING THE STUDY OF ENVIRONMENTAL INFLUENCES ON EPIGENOMICS AND TRANSCRIPTIONAL REGULATION, (5) CONDUCTING ENVIRONMENTAL PUBLIC HEALTH RESEARCH, INCLUDING IN AREAS OF ENVIRONMENTAL JUSTICE AND HEALTH DISPARITIES, THAT REQUIRES COMMUNITIES AS ACTIVE PARTICIPANTS IN ALL STAGES OF RESEARCH, DISSEMINATION, AND EVALUATION TO ADVANCE BOTH THE SCIENCE AND THE DEVELOPMENT OF PRACTICAL MATERIALS FOR USE IN COMMUNITIES, WITH A FOCUS ON TRANSLATING RESEARCH FINDINGS INTO TOOLS, MATERIALS, AND RESOURCES THAT CAN BE USED TO PREVENT, REDUCE, OR ELIMINATE ADVERSE HEALTH OUTCOMES CAUSED BY ENVIRONMENTAL EXPOSURES, (6) EXPANDING AND IMPROVING THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (7) EXPANDING AND IMPROVING THE STTR PROGRAM TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (8) PROVIDING SUPPORT FOR BROADLY BASED MULTI-DISCIPLINARY RESEARCH AND TRAINING PROGRAMS IN ENVIRONMENTAL HEALTH .THESE PROGRAMS INCLUDE THE ENVIRONMENTAL HEALTH SCIENCES CORE CENTERS , WHICH SERVE AS NATIONAL FOCAL POINTS AND RESOURCES FOR RESEARCH AND MANPOWER DEVELOPMENT. THROUGH THESE PROGRAMS, NIEHS EXPECTS TO ACHIEVE THE LONG-RANGE GOAL OF DEVELOPING NEW CLINICAL AND PUBLIC HEALTH APPLICATIONS TO IMPROVE DISEASE PREVENTION, DIAGNOSIS, AND THERAPY. ADDITIONAL CENTERS PROGRAMS DEVELOPED IN RECENT YEARS, INCLUDE THE CENTERS FOR OCEANS AND HUMAN HEALTH (CO-FUNDED WITH NSF), CHILDREN'S ENVIRONMENTAL HEALTH CENTERS (CO-FUNDED WITH US EPA) AND THE AUTISM CENTERS OF EXCELLENCE (CO-FUNDED WITH OTHER NIH INSTITUTES), AND THE HUMAN HEALTH EXPOSURE ANALYSIS RESOURCE (HHEAR) PROGRAM, (9) SUPPORTING RESEARCH TRAINING PROGRAMS WHICH SERVE TO INCREASE THE POOL OF TRAINED RESEARCH MANPOWER WITH NEEDED EXPERTISE IN THE ENVIRONMENTAL HEALTH SCIENCES THROUGH SUPPORT OF INDIVIDUAL AND INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS), (10) THE OUTSTANDING NEW ENVIRONMENTAL SCIENTIST PROGRAM WHICH PROVIDES FIRST TIME RESEARCH GRANT FUNDING TO OUTSTANDING JUNIOR SCIENTISTS IN THE FORMATIVE STAGES OF THEIR CAREER WHO ARE PROPOSING TO MAKE A LONG TERM COMMITMENT TO ENVIRONMENTAL HEALTH SCIENCES RESEARCH AND TO ADDRESS THE ADVERSE EFFECTS ON ENVIRONMENTAL EXPOSURES ON HUMAN BIOLOGY, HUMAN PATHOPHYSIOLOGY AND HUMAN DISEASE.

93.113 - Environmental Health

National Institute of Environmental Health Sciences (NIEHS) [HHS - NIH]

New York United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)