1 1852 207 ELECTRONIC CIGARETTES: THEIR CONSTITUENTS AND POTENTIAL LINKS TO ASTHMA. PURPOSE OF REVIEW: VAPING IS GAINING POPULARITY IN THE USA, PARTICULARLY AMONG TEENS AND YOUNG ADULTS. WHILE E-CIGS ARE COMMONLY REPRESENTED AS SAFER ALTERNATIVES TO TOBACCO CIGARETTES, LITTLE IS KNOWN REGARDING THE HEALTH EFFECTS OF THEIR SHORT- OR LONG-TERM USE, ESPECIALLY IN INDIVIDUALS WITH PRE-EXISTING RESPIRATORY DISEASES SUCH AS ASTHMA. FLAVORED E-CIG LIQUIDS (E-LIQUIDS) AND E-CIG AEROSOLS CONTAIN AIRWAY IRRITANTS AND TOXICANTS THAT HAVE BEEN IMPLICATED IN THE PATHOGENESIS AND WORSENING OF LUNG DISEASES. IN THIS REVIEW, WE WILL SUMMARIZE EXISTING DATA ON POTENTIAL HEALTH EFFECTS OF COMPONENTS PRESENT IN E-CIG AEROSOLS, SUCH AS PROPYLENE GLYCOL, VEGETABLE GLYCERIN, NICOTINE, AND FLAVORINGS, AND DISCUSS THEIR RELEVANCE IN THE CONTEXT OF ASTHMA. RECENT FINDINGS: RECENT SURVEY DATA INDICATE THAT ADOLESCENTS WITH ASTHMA HAD A HIGHER PREVALENCE OF CURRENT E-CIG USE (12.4%) COMPARED TO THEIR NON-ASTHMATICS PEERS (10.2%) AND CONVEYED POSITIVE BELIEFS ABOUT TOBACCO PRODUCTS, ESPECIALLY E-CIGS. SIMILARLY, A STUDY CONDUCTED AMONG HIGH SCHOOL STUDENTS FROM ONTARIO, CANADA, INDICATED A GREATER LIKELIHOOD OF E-CIG USE IN ASTHMATICS AS COMPARED TO THEIR NON-ASTHMATIC PEERS. AVAILABILITY OF DIFFERENT FLAVORINGS IS OFTEN CITED AS THE MAIN REASON AMONG YOUTH/ADOLESCENTS FOR TRYING E-CIGS OR SWITCHING FROM CIGARETTES TO E-CIGS. OCCUPATIONAL INHALATION OF SOME COMMON FOOD-SAFE FLAVORING AGENTS IS REPORTED TO CAUSE OCCUPATIONAL ASTHMA AND WORSEN ASTHMATIC SYMPTOMS. MOREOVER, WORKPLACE INHALATION EXPOSURES TO THE FLAVORING AGENT DIACETYL HAVE CAUSED IRREVERSIBLE OBSTRUCTIVE AIRWAY DISEASE IN HEALTHY WORKERS. ADDITIONALLY, RECENT STUDIES REPORT THAT THERMAL DECOMPOSITION OF PROPYLENE GLYCOL (PG) AND VEGETABLE GLYCERIN (VG), THE BASE CONSTITUENTS OF E-LIQUIDS, PRODUCES REACTIVE CARBONYLS, INCLUDING ACROLEIN, FORMALDEHYDE, AND ACETALDEHYDE, WHICH HAVE KNOWN RESPIRATORY TOXICITIES. FURTHERMORE, RECENT NICOTINE STUDIES IN RODENTS REVEAL THAT PRENATAL NICOTINE EXPOSURES LEAD TO EPIGENETIC REPROGRAMMING IN THE OFFSPRING, ABNORMAL LUNG DEVELOPMENT, AND MULTIGENERATIONAL TRANSMISSION OF ASTHMATIC-LIKE SYMPTOMS. COMPARISONS OF THE TOXICITY AND HEALTH EFFECTS OF E-CIGS AND CONVENTIONAL CIGARETTES OFTEN FOCUS ON TOXICANTS KNOWN TO BE PRESENT IN CIGARETTE SMOKE (CS) (I.E., FORMALDEHYDE, NITROSAMINES, ETC.), AS WELL AS SMOKING-ASSOCIATED CLINICAL ENDPOINTS, SUCH AS CANCER, BRONCHITIS, AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). HOWEVER, THIS APPROACH DISREGARDS POTENTIAL TOXICITY OF COMPONENTS UNIQUE TO FLAVORED E-CIGS, SUCH AS PG, VG, AND THE MANY DIFFERENT FLAVORING CHEMICALS, WHICH LIKELY INDUCE RESPIRATORY EFFECTS NOT USUALLY OBSERVED IN CIGARETTE SMOKERS. 2017 2 1358 29 DEVELOPMENT OF RATIOMETRIC ELECTROCHEMICAL MOLECULAR SWITCHES TO ASSAY ENDOGENOUS FORMALDEHYDE IN LIVE CELLS, WHOLE BLOOD AND CREATININE IN SALIVA. FORMALDEHYDE IS A REACTIVE CARBONYL SPECIES (RCS) THAT IS PRODUCED NATURALLY IN THE HUMAN BODY VIA METABOLIC AND EPIGENETIC BIOCHEMICAL PROCESSES, YET IN HIGH CONCENTRATIONS IS HIGHLY TOXIC TO THE ENVIRONMENT AS WELL AS TO LIVING ORGANISMS. THEREFORE, WE DESIGNED TWO RATIOMETRIC ELECTROCHEMICAL MOLECULAR REDOX PROBES, FORMALDEHYDE OXIDATIVE LATENT PROBE (FOLP) AND DIHYDROXY-FORMALDEHYDE OXIDATIVE LATENT PROBE (HFOLP), FOR THE SELECTIVE PROFILING OF ENDOGENOUS FORMALDEHYDE. FOLP AND HFOLP EACH UNDERWENT THE AZA-COPE REACTION WITH FORMALDEHYDE FOLLOWED BY HYDROLYSIS TO ELIMINATE UNMASK REDOX REPORTER N-ALKYLATED AMINOFERROCENE (AAF) TO MONITOR THEIR RESPONSE CURRENT. THE FOLP AND HFOLP SENSORS SHOWED BROAD DYNAMIC RANGES OF 0.12-1000 MUM AND 0.09-3 MM FOR FORMALDEHYDE WITH DETECTION LIMITS OF 48.2 NM AND 31.6 MUM, RESPECTIVELY. ALSO, SINCE FORMALDEHYDE IS THE BYPRODUCT OF BIOCHEMICAL REACTIONS FOR DETECTING CREATININE AND CREATININE IS AN IMPORTANT BIOMARKER FOR CHRONIC KIDNEY DISEASE (CKD), WE TESTED THE FOLP PROBE FOR ITS ABILITY TO MONITOR CREATININE. IT SUCCESSFULLY DID SO, AND THIS ABILITY WAS USED TO DEVELOP AN ELECTROCHEMICAL PLATFORM FOR THE QUANTIFICATION OF CREATININE; IT SHOWED A DYNAMIC RANGE OF 3.25-200 MUM AND A LIMIT OF DETECTION (1.3 MUM). IN ADDITION, THE FOLP-BASED ASSAY PLATFORM DELIVERED A RELIABLE ANALYTICAL PERFORMANCE FOR THE QUANTIFICATION OF FORMALDEHYDE IN HUMAN WHOLE BLOOD AND OF CREATININE IN SALIVA, AND ALSO FOR THE REAL-TIME MONITORING OF ENDOGENOUS FORMALDEHYDE SECRETION IN HELA CELLS. MOREOVER, THE CONCENTRATIONS DETERMINED USING OUR METHOD WERE FOUND TO BE CONSISTENT WITH THOSE DETERMINED USING FORMALDEHYDE AND CREATININE FLUOROMETRIC ASSAY KITS. 2021 3 2838 31 FORMALDEHYDE CARCINOGENICITY RESEARCH: 30 YEARS AND COUNTING FOR MODE OF ACTION, EPIDEMIOLOGY, AND CANCER RISK ASSESSMENT. FORMALDEHYDE IS A WIDELY USED HIGH PRODUCTION CHEMICAL THAT IS ALSO RELEASED AS A BYPRODUCT OF COMBUSTION, OFF-GASSING OF VARIOUS BUILDING PRODUCTS, AND AS A FIXATIVE FOR PATHOLOGISTS AND EMBALMERS. WHAT IS NOT OFTEN REALIZED IS THAT FORMALDEHYDE IS ALSO PRODUCED AS A NORMAL PHYSIOLOGIC CHEMICAL IN ALL LIVING CELLS. IN 1980, CHRONIC INHALATION OF HIGH CONCENTRATIONS OF FORMALDEHYDE WAS SHOWN TO BE CARCINOGENIC, INDUCING A HIGH INCIDENCE OF NASAL SQUAMOUS CELL CARCINOMAS IN RATS. SOME EPIDEMIOLOGIC STUDIES HAVE ALSO FOUND INCREASED NUMBERS OF NASOPHARYNGEAL CARCINOMA AND LEUKEMIA IN HUMANS EXPOSED TO FORMALDEHYDE THAT RESULTED IN FORMALDEHYDE BEING CONSIDERED A KNOWN HUMAN CARCINOGEN. THIS ARTICLE REVIEWS THE DATA FOR RODENT AND HUMAN CARCINOGENICITY, EARLY MODE OF ACTION STUDIES, MORE RECENT MOLECULAR STUDIES OF BOTH ENDOGENOUS AND EXOGENOUS DNA ADDUCTS, AND EPIGENETIC STUDIES. IT GOES ON TO DEMONSTRATE THE POWER OF THESE RESEARCH STUDIES TO PROVIDE CRITICAL DATA TO IMPROVE OUR ABILITY TO DEVELOP SCIENCE-BASED CANCER RISK ASSESSMENTS, INSTEAD OF DEFAULT APPROACHES. THE COMPLEXITY OF CONSTANT PHYSIOLOGIC EXPOSURE TO A KNOWN CARCINOGEN REQUIRES THAT NEW WAYS OF THINKING BE INCORPORATED INTO DETERMINATIONS OF CANCER RISK ASSESSMENT FOR FORMALDEHYDE, OTHER ENDOGENOUS CARCINOGENS, AND THE ROLE OF BACKGROUND ENDOGENOUS DNA DAMAGE AND MUTAGENESIS. 2013 4 5380 57 RECENT UPDATES ON BIOMARKERS OF EXPOSURE AND SYSTEMIC TOXICITY IN E-CIGARETTE USERS AND EVALI. ELECTRONIC NICOTINE DELIVERY SYSTEMS (ENDS), OR E-CIGARETTES, ARE EMERGING TOBACCO PRODUCTS THAT PRODUCE AEROSOLS BY HEATING E-LIQUIDS, WHICH MOST OFTEN CONSIST OF PROPYLENE GLYCOL AND VEGETABLE GLYCERIN ALONG WITH VARIOUS FLAVORING COMPOUNDS, BYPASSING THE COMBUSTION THAT OCCURS IN THE USE OF TRADITIONAL TOBACCO CIGARETTES. THESE PRODUCTS HAVE SEEN A DRASTIC INCREASE IN POPULARITY IN RECENT YEARS BOTH AS SMOKING CESSATION DEVICES AS WELL AS AMONG YOUNGER GENERATIONS, DUE IN LARGE PART TO THE WIDESPREAD PERCEPTION AMONG CONSUMERS THAT E-CIGS ARE SIGNIFICANTLY LESS HARMFUL TO HEALTH THAN TRADITIONAL TOBACCO CIGARETTES. DUE TO THE NOVELTY OF ENDS AS WELL AS THEIR RAPIDLY INCREASING USE, RESEARCH INTO BIOMARKERS OF E-CIG EXPOSURE AND TOXICITY HAVE LAGGED BEHIND THEIR POPULARITY, LEAVING IMPORTANT QUESTIONS ABOUT THEIR POTENTIAL TOXICITY UNANSWERED. RESEARCH INTO POTENTIAL BIOMARKERS OF ACUTE AND CHRONIC E-CIG USE, AND E-CIGARETTE- OR VAPING-ASSOCIATED LUNG INJURY IS NECESSARY FOR INFORMING BOTH CLINICAL AND REGULATORY DECISION-MAKING. WE AIM TO PROVIDE AN UPDATED REVIEW OF RECENT RESEARCH INTO POTENTIAL CIRCULATING, GENOMIC, TRANSCRIPTOMIC, AND EPIGENETIC BIOMARKERS OF EXPOSURE TO AND TOXICITY OF E-CIGS. WE ADDITIONALLY HIGHLIGHT RESEARCH AREAS THAT WARRANT ADDITIONAL STUDY TO GAIN A BETTER UNDERSTANDING OF HEALTH RISKS ASSOCIATED WITH ENDS USE, AS WELL AS TO PROVIDE VALIDATION OF EXISTING DATA AND METHODS FOR MEASURING AND ANALYZING E-CIG-ASSOCIATED BIOMARKERS IN HUMAN AND ANIMAL BIOFLUIDS, TISSUES, AND CELLS. THIS REVIEW ALSO HIGHLIGHTS ONGOING EFFORTS WITHIN THE WNY CENTER FOR RESEARCH ON FLAVORED TOBACCO FOR RESEARCH INTO NOVEL BIOMARKERS IN EXTRACELLULAR VESICLES THAT MAY BE ASSOCIATED WITH SHORT- AND LONG-TERM ENDS USE. 2021 5 6485 36 TOXICOLOGICAL MECHANISM OF INDIVIDUAL SUSCEPTIBILITY TO FORMALDEHYDE-INDUCED RESPIRATORY EFFECTS. UNDERSTANDING THE MECHANISMS OF INDIVIDUAL SUSCEPTIBILITY TO EXPOSURE TO ENVIRONMENTAL POLLUTANTS HAS BEEN A CHALLENGE IN HEALTH RISK ASSESSMENT. HERE, AN INTEGRATED APPROACH COMBINING A CRISPR SCREEN IN HUMAN CELLS AND EPIDEMIOLOGICAL ANALYSIS WAS DEVELOPED TO IDENTIFY THE INDIVIDUAL SUSCEPTIBILITY TO THE ADVERSE HEALTH EFFECTS OF AIR POLLUTANTS BY TAKING FORMALDEHYDE (FA) AND THE ASSOCIATED CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AS A CASE STUDY. AMONG THE PRIMARY HITS OF CRISPR SCREENING OF FA IN HUMAN A549 CELLS, HTR4 WAS THE ONLY GENE GENETICALLY ASSOCIATED WITH COPD SUSCEPTIBILITY IN GLOBAL POPULATIONS. HOWEVER, THE ASSOCIATION BETWEEN HTR4 AND FA-INDUCED RESPIRATORY TOXICITY IS UNKNOWN IN THE LITERATURE. ADVERSE OUTCOME PATHWAY (AOP) NETWORK ANALYSIS OF CRISPR SCREEN HITS PROVIDED A POTENTIAL MECHANISTIC LINK BETWEEN ACTIVATION OF HTR4 (MOLECULAR INITIATING EVENT) AND FA-INDUCED LUNG INJURY (ADVERSE OUTCOME). SYSTEMATIC TOXICOLOGY TESTS (IN VITRO AND ANIMAL EXPERIMENTS) WERE CONDUCTED TO REVEAL THE HTR4-INVOLVED BIOLOGICAL MECHANISMS UNDERLYING THE SUSCEPTIBILITY TO ADVERSE HEALTH EFFECTS OF FA. FUNCTIONALITY AND ENHANCED EXPRESSION OF HTR4 WERE REQUIRED FOR SUSCEPTIBILITY TO FA-INDUCED LUNG INJURY, AND FA-INDUCED EPIGENETIC CHANGES COULD RESULT IN ENHANCED EXPRESSION OF HTR4. SPECIFIC EPIGENETIC AND GENETIC CHARACTERISTICS OF HTR4 WERE ASSOCIATED WITH THE PROGRESSION AND PREVALENCE OF COPD, RESPECTIVELY, AND THESE GENETIC RISK FACTORS FOR COPD COULD BE POTENTIAL BIOMARKERS OF INDIVIDUAL SUSCEPTIBILITY TO ADVERSE RESPIRATORY EFFECTS OF FA. THESE BIOMARKERS COULD BE OF GREAT SIGNIFICANCE FOR DEFINING SUBPOPULATIONS SUSCEPTIBLE TO EXPOSURE TO FA AND REDUCING UNCERTAINTY IN THE NEXT-GENERATION HEALTH RISK ASSESSMENT OF AIR POLLUTANTS. OUR STUDY DELINEATED A NOVEL TOXICOLOGICAL PATHWAY MEDIATED BY HTR4 IN FA-INDUCED LUNG INJURY, WHICH COULD PROVIDE A MECHANISTIC UNDERSTANDING OF THE POTENTIAL BIOMARKERS OF INDIVIDUAL SUSCEPTIBILITY TO ADVERSE RESPIRATORY EFFECTS OF FA. 2022 6 4529 29 MULTIGENERATIONAL GRAPHENE OXIDE INTOXICATION RESULTS IN REPRODUCTION DISORDERS AT THE MOLECULAR LEVEL OF VITELLOGENIN PROTEIN EXPRESSION IN ACHETA DOMESTICUS. THE ANTHROPOGENIC ACTIVITIES MAY LEAD TO ACCUMULATION OF GRAPHENE OXIDE (GO) POLLUTION IN THE ENVIRONMENT. ORGANISMS EXPOSED TO CHRONIC OR MULTIGENERATIONAL GO INTOXICATION CAN PRESENT REPRODUCTION DEPLETION. VITELLOGENIN (VG) HAS BEEN USED AS A PARAMETER FOR EVALUATING FEMALE FERTILITY DUE TO ITS IMPORTANCE IN EMBRYO NUTRITION. IN THIS STUDY, WE USED A PROMISING MODEL ORGANISM, ACHETA DOMESTICUS, WHICH WAS INTOXICATED WITH GO IN FOOD FOR THREE GENERATIONS. THE AIM OF THE STUDY WAS TO INVESTIGATE THE PROCESS OF VG SYNTHESIS IN CRICKETS DEPENDING ON THE EXPOSURE TIME, GO CONCENTRATION, AND AGE OF THE FEMALES. THE RESULTS REVEALED THAT CHRONIC GO INTOXICATION HAD ADVERSE EFFECTS ON THE VG EXPRESSION PATTERN. THE 1ST GENERATION OF INSECTS SHOWING LOW VG EXPRESSION WAS MOST AFFECTED. THE 2ND GENERATION OF A. DOMESTICUS PRESENTED A HIGH VG EXPRESSION. THE LAST INVESTIGATED GENERATION SEEMED TO COPE WITH STRESS CAUSED BY GO, AND THE VG EXPRESSION WAS BALANCED. WE SUGGEST THAT THE EPIGENETIC MECHANISMS MAY PLAY A ROLE IN THE INFORMATION TRANSFER TO THE NEXT GENERATIONS ON HOW TO REACT TO THE RISK FACTOR AND KEEP REPRODUCTION AT A HIGH RATE. WE SUSPECT THAT CHRONIC GO INTOXICATION CAN DISTURB THE REGULAR FORMATION OF THE VG QUATERNARY STRUCTURE, RESULTING IN CONSEQUENCES FOR DEVELOPING AN EMBRYO. 2021 7 4822 31 OCHRATOXIN A: 50 YEARS OF RESEARCH. SINCE OCHRATOXIN A (OTA) WAS DISCOVERED, IT HAS BEEN UBIQUITOUS AS A NATURAL CONTAMINANT OF MOLDY FOOD AND FEED. THE MULTIPLE TOXIC EFFECTS OF OTA ARE A REAL THREAT FOR HUMAN BEINGS AND ANIMAL HEALTH. FOR EXAMPLE, OTA CAN CAUSE PORCINE NEPHROPATHY BUT CAN ALSO DAMAGE POULTRIES. HUMANS EXPOSED TO OTA CAN DEVELOP (NOTABLY BY INHALATION IN THE DEVELOPMENT OF ACUTE RENAL FAILURE WITHIN 24 H) A RANGE OF CHRONIC DISORDERS SUCH AS UPPER UROTHELIAL CARCINOMA. OTA PLAYS THE MAIN ROLE IN THE PATHOGENESIS OF SOME RENAL DISEASES INCLUDING BALKAN ENDEMIC NEPHROPATHY, KIDNEY TUMORS OCCURRING IN CERTAIN ENDEMIC REGIONS OF THE BALKAN PENINSULA, AND CHRONIC INTERSTITIAL NEPHROPATHY OCCURRING IN NORTHERN AFRICAN COUNTRIES AND LIKELY IN OTHER PARTS OF THE WORLD. OTA LEADS TO DNA ADDUCT FORMATION, WHICH IS KNOWN FOR ITS GENOTOXICITY AND CARCINOGENICITY. THE PRESENT ARTICLE DISCUSSES HOW RENAL CARCINOGENICITY AND NEPHROTOXICITY CAUSE BOTH OXIDATIVE STRESS AND DIRECT GENOTOXICITY. CAREFUL ANALYSES OF THE DATA SHOW THAT OTA CARCINOGENIC EFFECTS ARE DUE TO COMBINED DIRECT AND INDIRECT MECHANISMS (E.G., GENOTOXICITY, OXIDATIVE STRESS, EPIGENETIC FACTORS). ALTOGETHER THIS PROVIDES STRONG EVIDENCE THAT OTA CARCINOGENICITY CAN ALSO OCCUR IN HUMANS. 2016 8 363 41 AMBIENT AIR POLLUTION: HEALTH HAZARDS TO CHILDREN. AMBIENT AIR POLLUTION IS PRODUCED BY SOURCES INCLUDING VEHICULAR TRAFFIC, COAL-FIRED POWER PLANTS, HYDRAULIC FRACTURING, AGRICULTURAL PRODUCTION, AND FOREST FIRES. IT CONSISTS OF PRIMARY POLLUTANTS GENERATED BY COMBUSTION AND SECONDARY POLLUTANTS FORMED IN THE ATMOSPHERE FROM PRECURSOR GASES. AIR POLLUTION CAUSES AND EXACERBATES CLIMATE CHANGE, AND CLIMATE CHANGE WORSENS HEALTH EFFECTS OF AIR POLLUTION. INFANTS AND CHILDREN ARE UNIQUELY SENSITIVE TO AIR POLLUTION, BECAUSE THEIR ORGANS ARE DEVELOPING AND THEY HAVE HIGHER AIR PER BODY WEIGHT INTAKE. HEALTH EFFECTS LINKED TO AIR POLLUTION INCLUDE NOT ONLY EXACERBATIONS OF RESPIRATORY DISEASES BUT ALSO REDUCED LUNG FUNCTION DEVELOPMENT AND INCREASED ASTHMA INCIDENCE. ADDITIONAL OUTCOMES OF CONCERN INCLUDE PRETERM BIRTH, LOW BIRTH WEIGHT, NEURODEVELOPMENTAL DISORDERS, IQ LOSS, PEDIATRIC CANCERS, AND INCREASED RISKS FOR ADULT CHRONIC DISEASES. THESE EFFECTS ARE MEDIATED BY OXIDATIVE STRESS, CHRONIC INFLAMMATION, ENDOCRINE DISRUPTION, AND GENETIC AND EPIGENETIC MECHANISMS ACROSS THE LIFE SPAN. NATURAL EXPERIMENTS DEMONSTRATE THAT WITH INITIATIVES SUCH AS INCREASED USE OF PUBLIC TRANSPORTATION, BOTH AIR QUALITY AND COMMUNITY HEALTH IMPROVE. SIMILARLY, THE CLEAN AIR ACT HAS IMPROVED AIR QUALITY, ALTHOUGH EXPOSURE INEQUITIES PERSIST. OTHER EFFECTIVE STRATEGIES FOR REDUCING AIR POLLUTION INCLUDE ENDING RELIANCE ON COAL, OIL, AND GAS; REGULATING INDUSTRIAL EMISSIONS; REDUCING EXPOSURE WITH ATTENTION TO PROXIMITY OF RESIDENCES, SCHOOLS, AND CHILD CARE FACILITIES TO TRAFFIC; AND A GREATER AWARENESS OF THE AIR QUALITY INDEX. THIS POLICY REVIEWS BOTH SHORT- AND LONG-TERM HEALTH CONSEQUENCES OF AMBIENT AIR POLLUTION, ESPECIALLY IN RELATION TO DEVELOPMENTAL EXPOSURES. IT EXAMINES INDIVIDUAL, COMMUNITY, AND LEGISLATIVE STRATEGIES TO MITIGATE AIR POLLUTION. 2021 9 3712 36 INHALED POLLUTANTS: THE MOLECULAR SCENE BEHIND RESPIRATORY AND SYSTEMIC DISEASES ASSOCIATED WITH ULTRAFINE PARTICULATE MATTER. AIR POLLUTION OF ANTHROPOGENIC ORIGIN IS LARGELY FROM THE COMBUSTION OF BIOMASS (E.G., WOOD), FOSSIL FUELS (E.G., CARS AND TRUCKS), INCINERATORS, LANDFILLS, AGRICULTURAL ACTIVITIES AND TOBACCO SMOKE. AIR POLLUTION IS A COMPLEX MIXTURE THAT VARIES IN SPACE AND TIME, AND CONTAINS HUNDREDS OF COMPOUNDS INCLUDING VOLATILE ORGANIC COMPOUNDS (E.G., BENZENE), METALS, SULPHUR AND NITROGEN OXIDES, OZONE AND PARTICULATE MATTER (PM). PM(0.1) (ULTRAFINE PARTICLES (UFP)), THOSE PARTICLES WITH A DIAMETER LESS THAN 100 NM (INCLUDES NANOPARTICLES (NP)) ARE CONSIDERED ESPECIALLY DANGEROUS TO HUMAN HEALTH AND MAY CONTRIBUTE SIGNIFICANTLY TO THE DEVELOPMENT OF NUMEROUS RESPIRATORY AND CARDIOVASCULAR DISEASES SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND ATHEROSCLEROSIS. SOME OF THE PATHOGENIC MECHANISMS THROUGH WHICH PM(0.1) MAY CONTRIBUTE TO CHRONIC DISEASE IS THEIR ABILITY TO INDUCE INFLAMMATION, OXIDATIVE STRESS AND CELL DEATH BY MOLECULAR MECHANISMS THAT INCLUDE TRANSCRIPTION FACTORS SUCH AS NUCLEAR FACTOR KAPPAB (NF-KAPPAB) AND NUCLEAR FACTOR (ERYTHROID-DERIVED 2)-LIKE 2 (NRF2). EPIGENETIC MECHANISMS INCLUDING NON-CODING RNA (NCRNA) MAY ALSO CONTRIBUTE TOWARDS THE DEVELOPMENT OF CHRONIC DISEASE ASSOCIATED WITH EXPOSURE TO PM(0.1). THIS PAPER HIGHLIGHTS EMERGING MOLECULAR CONCEPTS ASSOCIATED WITH INHALATIONAL EXPOSURE TO PM(0.1) AND THEIR ABILITY TO CONTRIBUTE TO CHRONIC RESPIRATORY AND SYSTEMIC DISEASE. 2017 10 298 51 AIR POLLUTION AND AIRWAY DISEASE. EPIDEMIOLOGICAL AND TOXICOLOGICAL RESEARCH CONTINUES TO SUPPORT A LINK BETWEEN URBAN AIR POLLUTION AND AN INCREASED INCIDENCE AND/OR SEVERITY OF AIRWAY DISEASE. DETRIMENTAL EFFECTS OF OZONE (O(3)), NITROGEN DIOXIDE (NO(2)) AND PARTICULATE MATTER (PM), AS WELL AS TRAFFIC-RELATED POLLUTION AS A WHOLE, ON RESPIRATORY SYMPTOMS AND FUNCTION ARE WELL DOCUMENTED. NOT ONLY DO WE HAVE STRONG EPIDEMIOLOGICAL EVIDENCE OF A RELATIONSHIP BETWEEN AIR POLLUTION AND EXACERBATION OF ASTHMA AND RESPIRATORY MORBIDITY AND MORTALITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), BUT RECENT STUDIES, PARTICULARLY IN URBAN AREAS, HAVE SUGGESTED A ROLE FOR POLLUTANTS IN THE DEVELOPMENT OF BOTH ASTHMA AND COPD. SIMILARLY, WHILE PREVALENCE AND SEVERITY OF ATOPIC CONDITIONS APPEAR TO BE MORE COMMON IN URBAN COMPARED WITH RURAL COMMUNITIES, EVIDENCE IS EMERGING THAT TRAFFIC-RELATED POLLUTANTS MAY CONTRIBUTE TO THE DEVELOPMENT OF ALLERGY. FURTHERMORE, NUMEROUS EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES SUGGEST AN ASSOCIATION BETWEEN EXPOSURE TO NO(2) , O(3) , PM AND COMBUSTION PRODUCTS OF BIOMASS FUELS AND AN INCREASED SUSCEPTIBILITY TO AND MORBIDITY FROM RESPIRATORY INFECTION. GIVEN THE CONSIDERABLE CONTRIBUTION THAT TRAFFIC EMISSIONS MAKE TO URBAN AIR POLLUTION RESEARCHERS HAVE SOUGHT TO CHARACTERIZE THE RELATIVE TOXICITY OF TRAFFIC-RELATED PM POLLUTANTS. RECENT ADVANCES IN MECHANISMS IMPLICATED IN THE ASSOCIATION OF AIR POLLUTANTS AND AIRWAY DISEASE INCLUDE EPIGENETIC ALTERATION OF GENES BY COMBUSTION-RELATED POLLUTANTS AND HOW POLYMORPHISMS IN GENES INVOLVED IN ANTIOXIDANT PATHWAYS AND AIRWAY INFLAMMATION CAN MODIFY RESPONSES TO AIR POLLUTION EXPOSURES. OTHER INTERESTING EPIDEMIOLOGICAL OBSERVATIONS RELATED TO INCREASED HOST SUSCEPTIBILITY INCLUDE A POSSIBLE LINK BETWEEN CHRONIC PM EXPOSURE DURING CHILDHOOD AND VULNERABILITY TO COPD IN ADULTHOOD, AND THAT INFANTS SUBJECTED TO HIGHER PRENATAL LEVELS OF AIR POLLUTION MAY BE AT GREATER RISK OF DEVELOPING RESPIRATORY CONDITIONS. WHILE THE CHARACTERIZATION OF POLLUTANT COMPONENTS AND SOURCES PROMISE TO GUIDE POLLUTION CONTROL STRATEGIES, THE IDENTIFICATION OF SUSCEPTIBLE SUBPOPULATIONS WILL BE NECESSARY IF TARGETED THERAPY/PREVENTION OF POLLUTION-INDUCED RESPIRATORY DISEASES IS TO BE DEVELOPED. 2011 11 1140 25 CONCENTRATION OF FOLIC ACID (FA) IN SERUM OF JAPANESE PREGNANT WOMEN. OBJECTIVES EXPOSURE TO INORGANIC ARSENIC (IAS) IS A WORLD-WIDE HEALTH CONCERN. WE REPORTED THAT JAPANESE CHILDREN AND PREGNANT WOMEN ARE EXPOSED TO MODERATE LEVELS OF IAS THROUGH FOOD. REDUCING IAS CONTAMINATION FROM FOODS OF HIGH IAS IS AN IMPORTANT ISSUE UNIQUE IN JAPAN. INTEGRATED IAS IS METHYLATED TO LESS TOXIC ORGANIC FORMS, AND S-ADENOSYL-L-METHYONINE (SAM), A COMMON METHYL-DONOR OF DNA AND HISTONES, IS UTILIZED IN THIS PROCESS. CHRONIC CONSUMPTION OF SAM BY IAS METABOLISM DUE TO EXPOSURE TO IAS MIGHT ALTER THE EPIGENETIC MODIFICATION OF GENOME. THE SAM BIOSYNTHESIS PATHWAY IS DEPENDENT ON FOLATE CYCLE, AND IT IS POSSIBLE THAT INGESTION OF SUFFICIENT FOLIC ACID (FA) IS PROTECTIVE TO IAS INDUCED TOXICITY. METHODS IN THE COURSE OF OUR CROSS-SECTIONAL BODY BURDEN ANALYSES OF PB AND IAS IN JAPANESE CHILDREN AND PREGNANT WOMEN, TERMED "PBAS STUDY", FA CONCENTRATION IN SERUM OF 104 PREGNANT WOMEN WAS MEASURED. RESULTS MEAN (+/-SEM) OF SERUM FA CONCENTRATION WAS 15.8 +/- 1.3 (NG/ML). THERE ARE SIGNIFICANT NUMBER OF PEOPLE SHOWING VERY HIGH FA (>30 NG/ ML), AND LARGE FRACTION OF THEM WERE TAKING SUPPLEMENTS DAILY. CONCLUSIONS THESE RESULTS SUGGESTED THAT LEVEL OF FA INGESTION OF JAPANESE PREGNANT WOMEN IS HIGH FOR SUPPORTING NORMAL FETAL DEVELOPMENT. 2020 12 5174 41 PREDICTIVE AND PROGNOSTIC BIOMARKERS OF RESPIRATORY DISEASES DUE TO PARTICULATE MATTER EXPOSURE. AIR POLLUTION IS GETTING SEVERE AND CONCERNS ABOUT ITS TOXICITY EFFECTS ON AIRWAY AND LUNG DISEASE ARE ALSO INCREASING. PARTICULATE MATTER (PM) IS MAJOR COMPONENT OF AIR POLLUTANT. IT CAUSES RESPIRATORY DISEASES, SUCH AS ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, LUNG CANCER, AND SO ON. PM PARTICLES ENTER THE AIRWAY AND LUNG BY INHALATION, CAUSING DAMAGES TO THEM. ESPECIALLY, PM(2.5) CAN PENETRATE INTO THE ALVEOLUS AND PASS TO THE SYSTEMIC CIRCULATION. IT CAN AFFECT THE CARDIOPULMONARY SYSTEM AND CAUSE CARDIOPULMONARY DISORDERS. IN THIS REVIEW, WE FOCUSED ON PM-INDUCING TOXICITY MECHANISMS IN THE FRAMEWORK OF OXIDATIVE STRESS, INFLAMMATION, AND EPIGENETIC CHANGES. WE ALSO REVIEWED ITS CORRELATION WITH RESPIRATORY DISEASES. IN ADDITION, WE REVIEWED BIOMARKERS RELATED TO PM-INDUCED RESPIRATORY DISEASES. THESE BIOMARKERS MIGHT BE USED FOR DISEASE PREDICTION AND EARLY DIAGNOSIS. WITH RECENT TREND OF USING GENOMIC ANALYSIS TOOLS IN THE FIELD OF TOXICOGENOMICS, RESPIRATORY DISEASE BIOMARKERS ASSOCIATED WITH PM WILL BE CONTINUOUSLY INVESTIGATED. EFFECTIVE BIOMARKERS DERIVED FROM EARLIER STUDIES AND FURTHER STUDIES MIGHT BE UTILIZED TO REDUCE RESPIRATORY DISEASES. 2017 13 4135 42 MECHANISMS OF LUNG DAMAGE AND DEVELOPMENT OF COPD DUE TO HOUSEHOLD BIOMASS-SMOKE EXPOSURE: INFLAMMATION, OXIDATIVE STRESS, MICRORNAS, AND GENE POLYMORPHISMS. CHRONIC EXPOSURE TO INDOOR BIOMASS SMOKE FROM THE COMBUSTION OF SOLID ORGANIC FUELS IS A MAJOR CAUSE OF DISEASE BURDEN WORLDWIDE. ALMOST 3 BILLION PEOPLE USE SOLID FUELS SUCH AS WOOD, CHARCOAL, AND CROP RESIDUES FOR INDOOR COOKING AND HEATING, ACCOUNTING FOR APPROXIMATELY 50% OF ALL HOUSEHOLDS AND 90% OF RURAL HOUSEHOLDS GLOBALLY. BIOMASS SMOKE CONTAINS MANY HAZARDOUS POLLUTANTS, RESULTING IN HOUSEHOLD AIR POLLUTION (HAP) EXPOSURE THAT OFTEN EXCEEDS INTERNATIONAL STANDARDS. LONG-TERM BIOMASS-SMOKE EXPOSURE IS ASSOCIATED WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IN ADULTS, A LEADING CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE, CHRONIC BRONCHITIS, AND OTHER LUNG CONDITIONS. BIOMASS SMOKE-ASSOCIATED COPD DIFFERS FROM THE BEST-KNOWN CIGARETTE SMOKE-INDUCED COPD IN SEVERAL ASPECTS, SUCH AS A SLOWER DECLINE IN LUNG FUNCTION, GREATER AIRWAY INVOLVEMENT, AND LESS EMPHYSEMA, WHICH SUGGESTS A DIFFERENT PHENOTYPE AND PATHOPHYSIOLOGY. DESPITE THE HIGH BURDEN OF BIOMASS-ASSOCIATED COPD, THE MOLECULAR, GENETIC, AND EPIGENETIC MECHANISMS UNDERLYING ITS PATHOGENESIS ARE POORLY UNDERSTOOD. THIS REVIEW DESCRIBES THE PATHOGENIC MECHANISMS POTENTIALLY INVOLVED IN LUNG DAMAGE, THE DEVELOPMENT OF COPD ASSOCIATED WITH WOOD-DERIVED SMOKE EXPOSURE, AND THE INFLUENCE OF GENETIC AND EPIGENETIC FACTORS ON THE DEVELOPMENT OF THIS DISEASE. 2022 14 1352 43 DEVELOPMENT AND APPLICATION OF THE ADVERSE OUTCOME PATHWAY FRAMEWORK FOR UNDERSTANDING AND PREDICTING CHRONIC TOXICITY: I. CHALLENGES AND RESEARCH NEEDS IN ECOTOXICOLOGY. TO ELUCIDATE THE EFFECTS OF CHEMICALS ON POPULATIONS OF DIFFERENT SPECIES IN THE ENVIRONMENT, EFFICIENT TESTING AND MODELING APPROACHES ARE NEEDED THAT CONSIDER MULTIPLE STRESSORS AND ALLOW RELIABLE EXTRAPOLATION OF RESPONSES ACROSS SPECIES. AN ADVERSE OUTCOME PATHWAY (AOP) IS A CONCEPT THAT PROVIDES A FRAMEWORK FOR ORGANIZING KNOWLEDGE ABOUT THE PROGRESSION OF TOXICITY EVENTS ACROSS SCALES OF BIOLOGICAL ORGANIZATION THAT LEAD TO ADVERSE OUTCOMES RELEVANT FOR RISK ASSESSMENT. IN THIS PAPER, WE FOCUS ON EXPLORING HOW THE AOP CONCEPT CAN BE USED TO GUIDE RESEARCH AIMED AT IMPROVING BOTH OUR UNDERSTANDING OF CHRONIC TOXICITY, INCLUDING DELAYED TOXICITY AS WELL AS EPIGENETIC AND TRANSGENERATIONAL EFFECTS OF CHEMICALS, AND OUR ABILITY TO PREDICT ADVERSE OUTCOMES. A BETTER UNDERSTANDING OF THE INFLUENCE OF SUBTLE TOXICITY ON INDIVIDUAL AND POPULATION FITNESS WOULD SUPPORT A BROADER INTEGRATION OF SUBLETHAL ENDPOINTS INTO RISK ASSESSMENT FRAMEWORKS. DETAILED MECHANISTIC KNOWLEDGE WOULD FACILITATE THE DEVELOPMENT OF ALTERNATIVE TESTING METHODS AS WELL AS HELP PRIORITIZE HIGHER TIER TOXICITY TESTING. WE ARGUE THAT TARGETED DEVELOPMENT OF AOPS SUPPORTS BOTH OF THESE ASPECTS BY PROMOTING THE ELUCIDATION OF MOLECULAR MECHANISMS AND THEIR CONTRIBUTION TO RELEVANT TOXICITY OUTCOMES ACROSS BIOLOGICAL SCALES. WE FURTHER DISCUSS INFORMATION REQUIREMENTS AND CHALLENGES IN APPLICATION OF AOPS FOR CHEMICAL- AND SITE-SPECIFIC RISK ASSESSMENT AND FOR EXTRAPOLATION ACROSS SPECIES. WE PROVIDE RECOMMENDATIONS FOR POTENTIAL EXTENSION OF THE AOP FRAMEWORK TO INCORPORATE INFORMATION ON EXPOSURE, TOXICOKINETICS AND SITUATION-SPECIFIC ECOLOGICAL CONTEXTS, AND DISCUSS COMMON INTERFACES THAT CAN BE EMPLOYED TO COUPLE AOPS WITH COMPUTATIONAL MODELING APPROACHES AND WITH EVOLUTIONARY LIFE HISTORY THEORY. THE EXTENDED AOP FRAMEWORK CAN SERVE AS A VENUE FOR INTEGRATION OF KNOWLEDGE DERIVED FROM VARIOUS SOURCES, INCLUDING EMPIRICAL DATA AS WELL AS MOLECULAR, QUANTITATIVE AND EVOLUTIONARY-BASED MODELS DESCRIBING SPECIES RESPONSES TO TOXICANTS. THIS WILL ALLOW A MORE EFFICIENT APPLICATION OF AOP KNOWLEDGE FOR QUANTITATIVE CHEMICAL- AND SITE-SPECIFIC RISK ASSESSMENT AS WELL AS FOR EXTRAPOLATION ACROSS SPECIES IN THE FUTURE. 2015 15 1916 34 ENVIRONMENTAL AND OCCUPATIONAL EXPOSURE TO CHEMICALS AND TELOMERE LENGTH IN HUMAN STUDIES. TELOMERES ARE COMPLEXES OF TANDEM REPEATS OF DNA (5'-TTAGGG-3') AND PROTEIN THAT CAP EUKARYOTIC CHROMOSOMES AND PLAY A CRITICAL ROLE IN CHROMOSOME STABILITY. TELOMERES SHORTEN WITH AGING AND THIS PROCESS CAN BE ACCELERATED BY INCREASED OXIDATIVE STRESS AND EPISODES OF INFLAMMATION. EVIDENCE IS RAPIDLY GROWING THAT TELOMERE LENGTH (TL) MAY BE AFFECTED BY ENVIRONMENTAL CHEMICALS THAT HAVE FREQUENTLY BEEN ASSOCIATED WITH CHRONIC DISEASES. IN THIS ARTICLE, WE REVIEW THE PUBLISHED DATA ON TL IN RELATION TO ENVIRONMENTAL AND OCCUPATIONAL EXPOSURE TO SEVERAL CHEMICALS BASED ON OUR OWN AND OTHERS' STUDIES. THE ENVIRONMENTAL AND OCCUPATIONAL EXPOSURES ASSOCIATED WITH SHORTER TL INCLUDE TRAFFIC-RELATED AIR POLLUTION (IE, PARTICULATE MATTER (PM), BLACK CARBON (BC), AND BENZENE AND TOLUENE), POLYCYCLIC AROMATIC HYDROCARBONS (PAHS), N-NITROSAMINES, PESTICIDES, LEAD, EXPOSURE IN CAR MECHANICAL WORKSHOPS, AND HAZARDOUS WASTE EXPOSURE. ARSENIC, PERSISTENT ORGANIC POLLUTANTS (POPS) AND SHORT-TERM EXPOSURE TO PM ARE ASSOCIATED WITH LONGER TL. WE DISCUSS THE POSSIBLE REASONS FOR THE DIFFERENCES IN RESULTS, INCLUDING TIME- AND DOSE-RELATED ISSUES, STUDY DESIGN, AND POSSIBLE MECHANISMS INVOLVED IN TELOMERE REGULATION. WE ALSO DISCUSS THE FUTURE DIRECTIONS AND CHALLENGES FOR TL-RELATED ENVIRONMENTAL AND OCCUPATIONAL HEALTH RESEARCH, SUCH AS INVESTIGATION OF TL IN SUBPOPULATIONS OF BLOOD LEUKOCYTES, AND THE STUDY OF GENETIC AND EPIGENETIC FACTORS THAT MAY REGULATE TELOMERE INTEGRITY USING LONGITUDINAL DESIGNS. 2013 16 5623 38 SECOND-HAND SMOKE AND HUMAN LUNG CANCER. SINCE THE EARLY 1980S, THERE HAS BEEN GROWING CONCERN ABOUT POTENTIAL HEALTH CONSEQUENCES OF EXPOSURE TO SECOND-HAND SMOKE (SHS). DESPITE SHS BEING ESTABLISHED AS A RISK FACTOR FOR LUNG CANCER DEVELOPMENT, THE ESTIMATED RISK HAS REMAINED SMALL YET SOMEHOW DEBATABLE. HUMAN EXPOSURE TO SHS IS COMPLICATED BECAUSE OF TEMPORAL VARIABILITIES IN SOURCE, COMPOSITION, AND CONCENTRATION OF SHS. THE TEMPORALITY OF EXPOSURE TO SHS IS IMPORTANT FOR HUMAN LUNG CARCINOGENESIS WITH A LATENCY OF MANY YEARS. TO EXPLORE THE CAUSAL EFFECT OF SHS IN LUNG CARCINOGENESIS, EXPOSURE ASSESSMENTS SHOULD ESTIMATE CHRONIC EXPOSURE TO SHS ON AN INDIVIDUAL BASIS. HOWEVER, CONVENTIONAL EXPOSURE ASSESSMENT FOR SHS RELIES ON ONE-OFF OR SHORT-TERM MEASUREMENTS OF SHS INDICES. A MORE RELIABLE APPROACH WOULD BE TO USE BIOLOGICAL MARKERS THAT ARE SPECIFIC FOR SHS EXPOSURE AND PERTINENT TO LUNG CANCER. THIS APPROACH REQUIRES AN UNDERSTANDING OF THE UNDERLYING MECHANISMS THROUGH WHICH SHS COULD CONTRIBUTE TO LUNG CARCINOGENESIS. THIS REVIEW IS A SYNOPSIS OF RESEARCH ON SHS AND LUNG CANCER, WITH SPECIAL FOCUS ON HYPOTHETICAL MODES OF ACTION OF SHS FOR CARCINOGENESIS, INCLUDING GENOTOXIC AND EPIGENETIC EFFECTS. 2008 17 3901 40 LEAD (PB) AND NEURODEVELOPMENT: A REVIEW ON EXPOSURE AND BIOMARKERS OF EFFECT (BDNF, HDL) AND SUSCEPTIBILITY. LEAD (PB) IS A UBIQUITOUS ENVIRONMENTAL POLLUTANT AND A POTENT TOXIC COMPOUND. HUMANS ARE EXPOSED TO PB THROUGH INHALATION, INGESTION, AND SKIN CONTACT VIA FOOD, WATER, TOBACCO SMOKE, AIR, DUST, AND SOIL. PB ACCUMULATES IN BONES, BRAIN, LIVER AND KIDNEY. FETAL EXPOSURE OCCURS VIA TRANSPLACENTAL TRANSMISSION. THE MOST CRITICAL HEALTH EFFECTS ARE DEVELOPMENTAL NEUROTOXICITY IN INFANTS AND CARDIOVASCULAR EFFECTS AND NEPHROTOXICITY IN ADULTS. PB EXPOSURE HAS BEEN STEADILY DECREASING OVER THE PAST DECADES, BUT THERE ARE FEW RECENT EXPOSURE DATA FROM THE GENERAL EUROPEAN POPULATION; MOREOVER, NO SAFE PB LIMIT HAS BEEN SET. SENSITIVE BIOMARKERS OF EXPOSURE, EFFECT AND SUSCEPTIBILITY, THAT RELIABLY AND TIMELY INDICATE PB-ASSOCIATED TOXICITY ARE REQUIRED TO ASSESS HUMAN EXPOSURE-HEALTH RELATIONSHIPS IN A SITUATION OF LOW TO MODERATE EXPOSURE. THEREFORE, A SYSTEMATIC LITERATURE REVIEW BASED ON PUBMED ENTRIES PUBLISHED BEFORE JULY 2019 THAT ADDRESSED PB EXPOSURE AND BIOMARKERS OF EFFECT AND SUSCEPTIBILITY, NEURODEVELOPMENTAL TOXICITY, EPIGENETIC MODIFICATIONS, AND TRANSCRIPTOMICS WAS CONDUCTED. FINALLY INCLUDED WERE 58 ORIGINAL PAPERS ON PB EXPOSURE AND 17 STUDIES ON BIOMARKERS. THE BIOMARKERS THAT ARE LINKED TO PB EXPOSURE AND NEURODEVELOPMENT WERE GROUPED INTO EFFECT BIOMARKERS (SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AND SERUM/SALIVA CORTISOL), SUSCEPTIBILITY MARKERS (EPIGENETIC MARKERS AND GENE SEQUENCE VARIANTS) AND OTHER BIOMARKERS (SERUM HIGH-DENSITY LIPOPROTEIN (HDL), MATERNAL IRON (FE) AND CALCIUM (CA) STATUS). SERUM BDNF AND PLASMA HDL ARE POTENTIAL CANDIDATES TO BE FURTHER VALIDATED AS EFFECT MARKERS FOR ROUTINE USE IN HBM STUDIES OF PB, COMPLEMENTED BY MARKERS OF FE AND CA STATUS TO ALSO ADDRESS NUTRITIONAL INTERACTIONS RELATED TO NEURODEVELOPMENTAL DISORDERS. FOR SEVERAL MARKERS, A CAUSAL RELATIONSHIP WITH PB-INDUCED NEURODEVELOPMENTAL TOXICITY IS LIKELY. RESULTS ON BDNF ARE DISCUSSED IN RELATION TO ADVERSE OUTCOME PATHWAY (AOP) 13 ("CHRONIC BINDING OF ANTAGONIST TO N-METHYL-D-ASPARTATE RECEPTORS (NMDARS) DURING BRAIN DEVELOPMENT INDUCES IMPAIRMENT OF LEARNING AND MEMORY ABILITIES") OF THE AOP-WIKI. FURTHER STUDIES ARE NEEDED TO VALIDATE SENSITIVE, RELIABLE, AND TIMELY EFFECT BIOMARKERS, ESPECIALLY FOR LOW TO MODERATE PB EXPOSURE SCENARIOS. 2021 18 122 32 A SYSTEMATIC REVIEW ON FLUORIDE-INDUCED EPIGENETIC TOXICITY IN MAMMALS. FLUORIDE, ONE OF THE GLOBAL GROUNDWATER CONTAMINANTS, IS UBIQUITOUS IN OUR DAY-TO-DAY LIFE FROM VARIOUS NATURAL AND ANTHROPOGENIC SOURCES. NUMEROUS IN VITRO, IN VIVO, AND EPIDEMIOLOGICAL STUDIES ARE CONDUCTED TO UNDERSTAND THE EFFECT OF FLUORIDE ON BIOLOGICAL SYSTEMS. A LOW CONCENTRATION OF FLUORIDE IS REPORTED TO INCREASE ORAL HEALTH, WHEREAS CHRONIC EXPOSURE TO HIGHER CONCENTRATIONS CAUSES FLUORIDE TOXICITY (FLUOROSIS). IT INCLUDES DENTAL FLUOROSIS, SKELETAL FLUOROSIS, AND FLUORIDE TOXICITY IN SOFT TISSUES. THE MECHANISM OF FLUORIDE TOXICITY HAS BEEN REVIEWED EXTENSIVELY. HOWEVER, EPIGENETIC REGULATION IN FLUORIDE TOXICITY HAS NOT BEEN REVIEWED. THIS SYSTEMATIC REVIEW SUMMARIZES THE CURRENT KNOWLEDGE REGARDING FLUORIDE-INDUCED EPIGENETIC TOXICITY IN THE IN VITRO, IN VIVO, AND EPIDEMIOLOGICAL STUDIES IN MAMMALIAN SYSTEMS. WE EXAMINED FOUR DATABASES FOR THE ASSOCIATION BETWEEN EPIGENETICS AND FLUORIDE EXPOSURE. OUT OF 932 ARTICLES (AS OF 31 MARCH 2022), 39 MET OUR INCLUSION CRITERIA. MOST OF THE STUDIES FOCUSED ON DIFFERENT GENES, AND OVERALL, PRELIMINARY EVIDENCE FOR EPIGENETIC REGULATION OF FLUORIDE TOXICITY WAS IDENTIFIED. WE FURTHER HIGHLIGHT THE NEED FOR EPIGENOME STUDIES RATHER THAN CANDIDATE GENES AND PROVIDE RECOMMENDATIONS FOR FUTURE RESEARCH. OUR RESULTS INDICATE A CORRELATION BETWEEN FLUORIDE EXPOSURE AND EPIGENETIC PROCESSES. FURTHER STUDIES ARE WARRANTED TO ELUCIDATE AND CONFIRM THE MECHANISM OF EPIGENETIC ALTERATIONS MEDIATED FLUORIDE TOXICITY. 2022 19 4820 41 OCHRATOXIN A AS A POTENTIAL ETIOLOGIC FACTOR IN ENDEMIC NEPHROPATHY: LESSONS FROM TOXICITY STUDIES IN RATS. VARIOUS REPORTS SUGGEST THAT CHRONIC DIETARY EXPOSURE TO OCHRATOXIN A (OTA), A MYCOTOXIN FREQUENTLY DETECTED IN VARIOUS FOOD ITEMS MAY BE LINKED TO THE PATHOGENESIS OF ENDEMIC NEPHROPATHY, A CHRONIC TUBULOINTERSTITIAL KIDNEY DISEASE WHICH OCCURS IN GEOGRAPHICALLY LIMITED AREAS OF THE BALKAN REGION. OTA IS A POTENT NEPHROTOXIN AND RENAL CARCINOGEN. HOWEVER, THE PATHOLOGICAL LESIONS OBSERVED IN KIDNEYS OF RATS TREATED WITH OTA APPEAR BE RATHER DIFFERENT FROM THE CLINICAL AND PATHOLOGICAL CHARACTERISTICS OF ENDEMIC NEPHROPATHY. MOREOVER, INCREASING EVIDENCE SUGGESTS THAT OTA DOES NOT BIND TO DNA BUT INDUCES TUMORS BY AN EPIGENETIC, THRESHOLDED MECHANISM. THIS IMPLIES THAT THERE IS A DOSE BELOW WHICH NO ADVERSE HEALTH EFFECTS ARE EXPECTED TO OCCUR. BASED ON FOOD CONSUMPTION DATA AND OTA SERUM CONCENTRATIONS, IT APPEARS THAT HUMAN EXPOSURE - EVEN IN AREAS WITH RELATIVELY HIGH DIETARY EXPOSURE TO OTA SUCH AS ENDEMIC VILLAGES - IS SEVERAL ORDERS OF MAGNITUDE BELOW DOSES KNOWN TO CAUSE NEPHROTOXICITY AND TUMOR FORMATION IN LABORATORY ANIMALS. WHILE IT IS UNDOUBTEDLY IMPORTANT TO ENCOURAGE PREVENTION OF FOOD CONTAMINATION BY OTA AND OTHER MYCOTOXINS, THESE OBSERVATIONS SUGGEST THAT OTA IS NOT LIKELY TO BE AN ETIOLOGICAL FACTOR INVOLVED IN BEN AND INDICATE A NEED TO SEARCH FOR NEW CLUES FOR THE ETIOLOGY OF THIS ENDEMIC KIDNEY DISEASE. 2007 20 360 34 AMBIENT AIR POLLUTION AND BIOMARKERS OF HEALTH EFFECT. RECENTLY, THE AIR POLLUTION SITUATION OF OUR COUNTRY IS VERY SERIOUS ALONG WITH THE DEVELOPMENT OF URBANIZATION AND INDUSTRIALIZATION. STUDIES INDICATE THAT THE EXPOSURE OF AIR POLLUTION CAN CAUSE A RISE OF INCIDENCE AND MORTALITY OF MANY DISEASES, SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), ASTHMA, MYOCARDIAL INFARCTION, AND SO ON. HOWEVER, THERE IS NOW GROWING EVIDENCE SHOWING THAT SIGNIFICANT AIR POLLUTION EXPOSURES ARE ASSOCIATED WITH EARLY BIOMARKERS IN VARIOUS SYSTEMS OF THE BODY. IN ORDER TO BETTER PREVENT AND CONTROL THE DAMAGE EFFECT OF AIR POLLUTION, THIS ARTICLE SUMMARIZES COMPREHENSIVELY EPIDEMIOLOGICAL STUDIES ABOUT THE BAD EFFECTS ON THE BIOMARKERS OF RESPIRATORY SYSTEM, CARDIOVASCULAR SYSTEM, AND GENETIC AND EPIGENETIC SYSTEM EXPOSURE TO AMBIENT AIR POLLUTION. 2017