1 4626 116 NEURODEVELOPMENTAL DISORDERS AND ENVIRONMENTAL TOXICANTS: EPIGENETICS AS AN UNDERLYING MECHANISM. THE INCREASING PREVALENCE OF NEURODEVELOPMENTAL DISORDERS, ESPECIALLY AUTISM SPECTRUM DISORDERS (ASD) AND ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD), CALLS FOR MORE RESEARCH INTO THE IDENTIFICATION OF ETIOLOGIC AND RISK FACTORS. THE DEVELOPMENTAL ORIGIN OF HEALTH AND DISEASE (DOHAD) HYPOTHESIZES THAT THE ENVIRONMENT DURING FETAL AND CHILDHOOD DEVELOPMENT AFFECTS THE RISK FOR MANY CHRONIC DISEASES IN LATER STAGES OF LIFE, INCLUDING NEURODEVELOPMENTAL DISORDERS. EPIGENETICS, A TERM DESCRIBING MECHANISMS THAT CAUSE CHANGES IN THE CHROMOSOME STATE WITHOUT AFFECTING DNA SEQUENCES, IS SUGGESTED TO BE THE UNDERLYING MECHANISM, ACCORDING TO THE DOHAD HYPOTHESIS. MOREOVER, MANY NEURODEVELOPMENTAL DISORDERS ARE ALSO RELATED TO EPIGENETIC ABNORMALITIES. EXPERIMENTAL AND EPIDEMIOLOGICAL STUDIES SUGGEST THAT EXPOSURE TO PRENATAL ENVIRONMENTAL TOXICANTS IS ASSOCIATED WITH NEURODEVELOPMENTAL DISORDERS. IN ADDITION, THERE IS ALSO EVIDENCE THAT ENVIRONMENTAL TOXICANTS CAN RESULT IN EPIGENETIC ALTERATIONS, NOTABLY DNA METHYLATION. IN THIS REVIEW, WE FIRST FOCUS ON THE RELATIONSHIP BETWEEN NEURODEVELOPMENTAL DISORDERS AND ENVIRONMENTAL TOXICANTS, IN PARTICULAR MATERNAL SMOKING, PLASTIC-DERIVED CHEMICALS (BISPHENOL A AND PHTHALATES), PERSISTENT ORGANIC POLLUTANTS, AND HEAVY METALS. WE THEN REVIEW STUDIES SHOWING THE EPIGENETIC EFFECTS OF THOSE ENVIRONMENTAL FACTORS IN HUMANS THAT MAY AFFECT NORMAL NEURODEVELOPMENT. 2017 2 363 34 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 3 5450 35 REPRODUCTIVE TOXICITY OF COMBINED EFFECTS OF ENDOCRINE DISRUPTORS ON HUMAN REPRODUCTION. CONFLUENCE OF ENVIRONMENTAL, GENETIC, AND LIFESTYLE VARIABLES IS RESPONSIBLE FOR DETERIORATION OF HUMAN FECUNDITY. ENDOCRINE DISRUPTORS OR ENDOCRINE DISRUPTING CHEMICALS (EDCS) MAY BE FOUND IN A VARIETY OF FOODS, WATER, AIR, BEVERAGES, AND TOBACCO SMOKE. IT HAS BEEN DEMONSTRATED IN EXPERIMENTAL INVESTIGATIONS THAT A WIDE RANGE OF ENDOCRINE DISRUPTING CHEMICALS HAVE NEGATIVE EFFECTS ON HUMAN REPRODUCTIVE FUNCTION. HOWEVER, EVIDENCE ON THE REPRODUCTIVE CONSEQUENCES OF HUMAN EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS IS SPARSE AND/OR CONFLICTING IN THE SCIENTIFIC LITERATURE. THE COMBINED TOXICOLOGICAL ASSESSMENT IS A PRACTICAL METHOD FOR ASSESSING THE HAZARDS OF COCKTAILS OF CHEMICALS, CO-EXISTING IN THE ENVIRONMENT. THE CURRENT REVIEW PROVIDES A COMPREHENSIVE OVERVIEW OF STUDIES EMPHASIZING THE COMBINED TOXICITY OF ENDOCRINE DISRUPTING CHEMICALS ON HUMAN REPRODUCTION. ENDOCRINE DISRUPTING CHEMICALS INTERACT WITH EACH OTHER TO DISRUPT THE DIFFERENT ENDOCRINE AXES, RESULTING IN SEVERE GONADAL DYSFUNCTIONS. TRANSGENERATIONAL EPIGENETIC EFFECTS HAVE ALSO BEEN INDUCED IN GERM CELLS, MOSTLY THROUGH DNA METHYLATION AND EPIMUTATIONS. SIMILARLY, AFTER ACUTE OR CHRONIC EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS COMBINATIONS, INCREASED OXIDATIVE STRESS (OS), ELEVATED ANTIOXIDANT ENZYMATIC ACTIVITY, DISRUPTED REPRODUCTIVE CYCLE, AND REDUCED STEROIDOGENESIS ARE OFTEN REPORTED CONSEQUENCES. THE ARTICLE ALSO DISCUSSES THE CONCENTRATION ADDITION (CA) AND INDEPENDENT ACTION (IA) PREDICTION MODELS, WHICH REVEAL THE IMPORTANCE OF VARIOUS SYNERGISTIC ACTIONS OF ENDOCRINE DISRUPTING CHEMICALS MIXTURES. MORE CRUCIALLY, THIS EVIDENCE-BASED STUDY ADDRESSES THE RESEARCH LIMITATIONS AND INFORMATION GAPS, AS WELL AS PARTICULARLY PRESENTS THE FUTURE RESEARCH VIEWS ON COMBINED ENDOCRINE DISRUPTING CHEMICALS TOXICITY ON HUMAN REPRODUCTION. 2023 4 1767 41 EARLY-LIFE EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS AND LATER-LIFE HEALTH OUTCOMES: AN EPIGENETIC BRIDGE? A GROWING BODY OF EVIDENCE DEMONSTRATES THAT ADVERSE EVENTS EARLY IN DEVELOPMENT, AND PARTICULARLY DURING INTRAUTERINE LIFE, MAY PROGRAM RISKS FOR DISEASES IN ADULT LIFE. INCREASING EVIDENCE HAS BEEN ACCUMULATED INDICATING THE IMPORTANT ROLE OF EPIGENETIC REGULATION INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS AND MIRNAS IN DEVELOPMENTAL PROGRAMMING. AMONG THE ENVIRONMENTAL FACTORS WHICH PLAY AN IMPORTANT ROLE IN PROGRAMMING OF CHRONIC PATHOLOGIES, THE ENDOCRINE-DISRUPTING CHEMICALS (EDCS) THAT HAVE ESTROGENIC, ANTI-ESTROGENIC, AND ANTI-ANDROGENIC ACTIVITY ARE OF SPECIFIC CONCERN BECAUSE THE DEVELOPING ORGANISM IS EXTREMELY SENSITIVE TO PERTURBATION BY SUBSTANCES WITH HORMONE-LIKE ACTIVITY. AMONG EDCS, THERE ARE MANY SUBSTANCES THAT ARE CONSTANTLY PRESENT IN THE MODERN HUMAN ENVIRONMENT OR ARE IN WIDESPREAD USE, INCLUDING DIOXIN AND DIOXIN-LIKE COMPOUNDS, PHTHALATES, AGRICULTURAL PESTICIDES, POLYCHLORINATED BIPHENYLS, INDUSTRIAL SOLVENTS, PHARMACEUTICALS, AND HEAVY METALS. APART FROM THEIR COMMON ENDOCRINE ACTIVE PROPERTIES, SEVERAL EDCS HAVE BEEN SHOWN TO DISRUPT DEVELOPMENTAL EPIGENOMIC PROGRAMMING. THE PURPOSE OF THIS REVIEW IS TO PROVIDE A SUMMARY OF RECENT RESEARCH FINDINGS WHICH INDICATE THAT EXPOSURE TO EDCS DURING IN-UTERO AND/OR NEONATAL DEVELOPMENT CAN CAUSE LONG-TERM HEALTH OUTCOMES VIA MECHANISMS OF EPIGENETIC MEMORY. 2014 5 4805 35 OBESITY AND METABOLIC COMORBIDITIES: ENVIRONMENTAL DISEASES? OBESITY AND METABOLIC COMORBIDITIES REPRESENT INCREASING HEALTH PROBLEMS. ENDOCRINE DISRUPTING COMPOUNDS (EDCS) ARE EXOGENOUS AGENTS THAT CHANGE ENDOCRINE FUNCTION AND CAUSE ADVERSE HEALTH EFFECTS. MOST EDCS ARE SYNTHETIC CHEMICALS; SOME ARE NATURAL FOOD COMPONENTS AS PHYTOESTROGENS. PEOPLE ARE EXPOSED TO COMPLEX MIXTURES OF CHEMICALS THROUGHOUT THEIR LIVES. EDCS IMPACT HORMONE-DEPENDENT METABOLIC SYSTEMS AND BRAIN FUNCTION. LABORATORY AND HUMAN STUDIES PROVIDE COMPELLING EVIDENCE THAT HUMAN CHEMICAL CONTAMINATION CAN PLAY A ROLE IN OBESITY EPIDEMIC. CHEMICAL EXPOSURES MAY INCREASE THE RISK OF OBESITY BY ALTERING THE DIFFERENTIATION OF ADIPOCYTES. EDCS CAN ALTER METHYLATION PATTERNS AND NORMAL EPIGENETIC PROGRAMMING IN CELLS. OXIDATIVE STRESS MAY BE INDUCED BY MANY OF THESE CHEMICALS, AND ACCUMULATING EVIDENCE INDICATES THAT IT PLAYS IMPORTANT ROLES IN THE ETIOLOGY OF CHRONIC DISEASES. THE INDIVIDUAL SENSITIVITY TO CHEMICALS IS VARIABLE, DEPENDING ON ENVIRONMENT AND ABILITY TO METABOLIZE HAZARDOUS CHEMICALS. A NUMBER OF GENES, ESPECIALLY THOSE REPRESENTING ANTIOXIDANT AND DETOXIFICATION PATHWAYS, HAVE POTENTIAL APPLICATION AS BIOMARKERS OF RISK ASSESSMENT. THE POTENTIAL HEALTH EFFECTS OF COMBINED EXPOSURES MAKE THE RISK ASSESSMENT PROCESS MORE COMPLEX COMPARED TO THE ASSESSMENT OF SINGLE CHEMICALS. TECHNIQUES AND METHODS NEED TO BE FURTHER DEVELOPED TO FILL DATA GAPS AND INCREASE THE KNOWLEDGE ON HARMFUL EXPOSURE COMBINATIONS. 2013 6 1644 37 DOES THE ENVIRONMENT AFFECT MENOPAUSE? A REVIEW OF THE EFFECTS OF ENDOCRINE DISRUPTING CHEMICALS ON MENOPAUSE. ENDOCRINE DISRUPTING CHEMICALS ARE WIDELY DISTRIBUTED IN OUR ENVIRONMENT. HUMANS ARE EXPOSED TO THESE COMPOUNDS NOT ONLY THROUGH THEIR OCCUPATIONS, BUT ALSO THROUGH DIETARY CONSUMPTION AND EXPOSURE TO CONTAMINATED WATER, PERSONAL CARE PRODUCTS AND TEXTILES. CHEMICALS THAT ARE PERSISTENT IN THE BODY AND IN OUR ENVIRONMENT INCLUDE DIOXINS AND POLYCHLORINATED BIPHENYLS. NON-PERSISTENT CHEMICALS INCLUDING BISPHENOL A, PHTHALATES AND PARABENS ARE EQUALLY AS IMPORTANT BECAUSE THEY ARE UBIQUITOUS IN OUR ENVIRONMENT. HEAVY METALS, INCLUDING LEAD AND CADMIUM, CAN ALSO HAVE ENDOCRINE DISRUPTING PROPERTIES. ALTHOUGH DIFFICULT TO STUDY DUE TO THEIR VARIETY OF SOURCES OF EXPOSURES AND MECHANISMS OF ACTION, THESE CHEMICALS HAVE BEEN ASSOCIATED WITH EARLY MENOPAUSE, INCREASED FREQUENCY OF VASOMOTOR SYMPTOMS, ALTERED STEROID HORMONE LEVELS AND MARKERS OF DIMINISHED OVARIAN RESERVE. UNDERSTANDING THE IMPACTS OF THESE EXPOSURES IS IMPORTANT GIVEN THE POTENTIAL FOR EPIGENETIC MODIFICATION, WHICH CAN ALTER GENE FUNCTION AND RESULT IN MULTI-GENERATIONAL EFFECTS. THIS REVIEW SUMMARIZES FINDINGS IN HUMANS AND ANIMALS OR CELL-BASED MODELS FROM THE PAST DECADE OF RESEARCH. CONTINUED RESEARCH IS NEEDED TO ASSESS THE EFFECTS OF MIXTURES OF CHEMICALS, CHRONIC EXPOSURES AND NEW COMPOUNDS THAT ARE CONTINUOUSLY BEING DEVELOPED AS REPLACEMENTS FOR TOXIC CHEMICALS THAT ARE BEING PHASED OUT. 2023 7 360 30 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 8 1352 35 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 9 298 48 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 10 1157 33 CONTAMINANT METALS AS CARDIOVASCULAR RISK FACTORS: A SCIENTIFIC STATEMENT FROM THE AMERICAN HEART ASSOCIATION. EXPOSURE TO ENVIRONMENTAL POLLUTANTS IS LINKED TO INCREASED RISK OF CARDIOVASCULAR DISEASE. BEYOND THE EXTENSIVE EVIDENCE FOR PARTICULATE AIR POLLUTION, ACCUMULATING EVIDENCE SUPPORTS THAT EXPOSURE TO NONESSENTIAL METALS SUCH AS LEAD, CADMIUM, AND ARSENIC IS A SIGNIFICANT CONTRIBUTOR TO CARDIOVASCULAR DISEASE WORLDWIDE. HUMANS ARE EXPOSED TO METALS THROUGH AIR, WATER, SOIL, AND FOOD AND EXTENSIVE INDUSTRIAL AND PUBLIC USE. CONTAMINANT METALS INTERFERE WITH CRITICAL INTRACELLULAR REACTIONS AND FUNCTIONS LEADING TO OXIDATIVE STRESS AND CHRONIC INFLAMMATION THAT RESULT IN ENDOTHELIAL DYSFUNCTION, HYPERTENSION, EPIGENETIC DYSREGULATION, DYSLIPIDEMIA, AND CHANGES IN MYOCARDIAL EXCITATION AND CONTRACTILE FUNCTION. LEAD, CADMIUM, AND ARSENIC HAVE BEEN LINKED TO SUBCLINICAL ATHEROSCLEROSIS, CORONARY ARTERY STENOSIS, AND CALCIFICATION AS WELL AS TO INCREASED RISK OF ISCHEMIC HEART DISEASE AND STROKE, LEFT VENTRICULAR HYPERTROPHY AND HEART FAILURE, AND PERIPHERAL ARTERY DISEASE. EPIDEMIOLOGICAL STUDIES SHOW THAT EXPOSURE TO LEAD, CADMIUM, OR ARSENIC IS ASSOCIATED WITH CARDIOVASCULAR DEATH MOSTLY ATTRIBUTABLE TO ISCHEMIC HEART DISEASE. PUBLIC HEALTH MEASURES REDUCING METAL EXPOSURE ARE ASSOCIATED WITH REDUCTIONS IN CARDIOVASCULAR DISEASE DEATH. POPULATIONS OF COLOR AND LOW SOCIOECONOMIC MEANS ARE MORE COMMONLY EXPOSED TO METALS AND THEREFORE AT GREATER RISK OF METAL-INDUCED CARDIOVASCULAR DISEASE. TOGETHER WITH STRENGTHENING PUBLIC HEALTH MEASURES TO PREVENT METAL EXPOSURES, DEVELOPMENT OF MORE SENSITIVE AND SELECTIVE MEASUREMENT MODALITIES, CLINICAL MONITORING OF METAL EXPOSURES, AND THE DEVELOPMENT OF METAL CHELATION THERAPIES COULD FURTHER DIMINISH THE BURDEN OF CARDIOVASCULAR DISEASE ATTRIBUTABLE TO METAL EXPOSURE. 2023 11 3566 33 IMPACT OF HEAVY METALS ON THE FEMALE REPRODUCTIVE SYSTEM. INTRODUCTION: IT HAS BEEN RECOGNIZED THAT ENVIRONMENTAL POLLUTION CAN AFFECT THE QUALITY OF HEALTH OF THE HUMAN POPULATION. HEAVY METALS ARE AMONG THE GROUP OF HIGHLY EMITTED CONTAMINANTS AND THEIR ADVERSE EFFECT OF LIVING ORGANISMS HAS BEEN WIDELY STUDIED IN RECENT DECADES. LIFESTYLE AND QUALITY OF THE AMBIENT ENVIRONMENT ARE AMONG THESE FACTORS WHICH CAN MAINLY CONTRIBUTE TO THE HEAVY METALS EXPOSURE IN HUMANS. OBJECTIVE: A REVIEW OF LITERATURE LINKING HEAVY METALS AND THE FEMALE REPRODUCTIVE SYSTEM AND DESCRIPTION OF THE POSSIBLE ASSOCIATIONS WITH EMISSION AND EXPOSURE OF HEAVY METALS AND IMPAIRMENTS OF FEMALE REPRODUCTIVE SYSTEM ACCORDING TO CURRENT KNOWLEDGE. RESULTS: THE POTENTIAL HEALTH DISORDERS CAUSED BY CHRONIC OR ACUTE HEAVY METALS TOXICITY INCLUDE IMMUNODEFICIENCY, OSTEOPOROSIS, NEURODEGENERATION AND ORGAN FAILURES. POTENTIAL LINKAGES OF HEAVY METALS CONCENTRATION FOUND IN DIFFERENT HUMAN ORGANS AND BLOOD WITH OESTROGEN-DEPENDENT DISEASES SUCH AS BREAST CANCER, ENDOMETRIAL CANCER, ENDOMETRIOSIS AND SPONTANEOUS ABORTIONS, AS WELL AS PRE-TERM DELIVERIES, STILLBIRTHS AND HYPOTROPHY, HAVE ALSO BEEN REPORTED. CONCLUSIONS: ENVIRONMENTAL DETERIORATION CAN LEAD TO THE ELEVATED RISK OF HUMAN EXPOSURE TO HEAVY METALS, AND CONSEQUENTLY, HEALTH IMPLICATIONS INCLUDING DISTURBANCES IN REPRODUCTION. IT IS THEREFORE IMPORTANT TO CONTINUE THE INVESTIGATIONS ON METAL-INDUCED MECHANISMS OF FERTILITY IMPAIRMENT ON THE GENETIC, EPIGENETIC AND BIOCHEMICAL LEVEL. 2015 12 1919 42 ENVIRONMENTAL ENDOCRINE DISRUPTORS: NEW DIABETOGENS? THE PREVALENCE OF TYPE-2 DIABETES HAS DRAMATICALLY INCREASED WORLDWIDE DURING THE LAST FEW DECADES. WHILE LIFESTYLE FACTORS (SEDENTARINESS, NOXIOUS FOOD), TOGETHER WITH GENETIC SUSCEPTIBILITY, ARE WELL-KNOWN ACTORS, THERE IS ACCUMULATING EVIDENCE SUGGESTING THAT ENDOCRINE DISRUPTING CHEMICALS (EDCS) MAY ALSO PLAY A PATHOPHYSIOLOGICAL ROLE IN THE OCCURRENCE OF METABOLIC DISEASES. BOTH EXPERIMENTAL AND EPIDEMIOLOGICAL EVIDENCE SUPPORT A ROLE FOR EARLY AND CHRONIC EXPOSURE TO LOW DOSES OF CHEMICAL POLLUTANTS WITH ENDOCRINE AND METABOLIC DISRUPTING EFFECTS. MOST ARE PRESENT IN THE FOOD CHAIN AND ACCUMULATE IN THE FAT MASS AFTER ABSORPTION. IN RODENTS, BISPHENOL A STIMULATES SYNTHESIS AND SECRETION OF PANCREATIC BETA CELLS AND DISTURBS INSULIN SIGNALING IN LIVER, MUSCLE AND ADIPOSE TISSUE THROUGH EPIGENETIC CHANGES LEADING TO INSULIN RESISTANCE AND BETA CELL IMPAIRMENT. IN HUMANS, EPIDEMIOLOGICAL REPORTS SHOW STATISTICAL LINK BETWEEN EXPOSURE TO PESTICIDES, POLYCHLORINATED BISPHENYLS, BISPHENOL A, PHTHALATES, DIOXINS OR AROMATIC POLYCYCLIC HYDROCARBIDES OR HEAVY METALS AND DT2 AFTER ACUTE ACCIDENTAL RELEASES OR EARLY IN LIFE AND/OR CHRONIC, LOW DOSES EXPOSURE. MORE PROSPECTIVE, LONGITUDINAL STUDIES ARE NEEDED TO DETERMINE THE IMPORTANCE OF SUCH ENVIRONMENTAL RISK FACTORS. 2017 13 1857 28 ELIMINATION OF PERSISTENT TOXICANTS FROM THE HUMAN BODY. THERE IS COMPELLING EVIDENCE THAT VARIOUS CHEMICAL AGENTS ARE IMPORTANT DETERMINANTS OF MYRIAD HEALTH AFFLICTIONS--SEVERAL XENOBIOTICS HAVE THE POTENTIAL TO DISRUPT REPRODUCTIVE, DEVELOPMENTAL, AND NEUROLOGICAL PROCESSES AND SOME AGENTS IN COMMON USE HAVE CARCINOGENIC, EPIGENETIC, ENDOCRINE-DISRUPTING, AND IMMUNE-ALTERING ACTION. SOME TOXICANTS APPEAR TO HAVE BIOLOGICAL EFFECT AT MINISCULE LEVELS AND CERTAIN CHEMICAL COMPOUNDS ARE PERSISTENT AND BIOACCUMULATIVE WITHIN THE HUMAN BODY. DESPITE ESCALATING PUBLIC HEALTH MEASURES TO PRECLUDE FURTHER EXPOSURES, MANY PEOPLE THROUGHOUT THE WORLD HAVE ALREADY ACCRUED A SIGNIFICANT BODY BURDEN OF TOXICANTS, PLACING THEM AT POTENTIAL HEALTH RISK. AS A RESULT, INCREASING DISCUSSION IS UNDERWAY ABOUT POSSIBLE INTERVENTIONS TO FACILITATE ELIMINATION OF PERSISTENT TOXICANTS FROM THE HUMAN ORGANISM IN ORDER TO OBVIATE HEALTH AFFLICTION AND TO POTENTIALLY AMELIORATE CHRONIC DEGENERATIVE ILLNESS. AN OVERVIEW OF THE CLINICAL ASPECTS OF DETOXIFICATION IS PRESENTED WITH DISCUSSION OF ESTABLISHED AND EMERGING INTERVENTIONS FOR THE ELIMINATION OF PERSISTENT XENOBIOTICS. POTENTIAL THERAPIES TO CIRCUMVENT ENTEROHEPATIC RECIRCULATION AND A CASE REPORT HIGHLIGHTING A CLINICAL OUTCOME ASSOCIATED WITH DETOXIFICATION ARE ALSO PRESENTED FOR CONSIDERATION. 2011 14 5254 43 PROGRAMMING OF RESPIRATORY HEALTH IN CHILDHOOD: INFLUENCE OF OUTDOOR AIR POLLUTION. PURPOSE OF REVIEW: THIS OVERVIEW HIGHLIGHTS RECENT EXPERIMENTAL AND EPIDEMIOLOGICAL EVIDENCE FOR THE PROGRAMMING EFFECTS OF OUTDOOR AIR POLLUTION EXPOSURES DURING EARLY DEVELOPMENT ON LUNG FUNCTION AND CHRONIC RESPIRATORY DISORDERS, SUCH AS ASTHMA AND RELATED ALLERGIC DISORDERS. RECENT FINDINGS: AIR POLLUTANTS MAY IMPACT ANATOMY AND/OR PHYSIOLOGICAL FUNCTIONING OF THE LUNG AND INTERRELATED SYSTEMS. PROGRAMMING EFFECTS MAY RESULT FROM POLLUTANT-INDUCED SHIFTS IN A NUMBER OF MOLECULAR, CELLULAR, AND PHYSIOLOGICAL STATES AND THEIR INTERACTING SYSTEMS. SPECIFIC KEY REGULATORY SYSTEMS SUSCEPTIBLE TO PROGRAMMING MAY INFLUENCE LUNG DEVELOPMENT AND VULNERABILITY TO RESPIRATORY DISEASES, INCLUDING BOTH CENTRAL AND PERIPHERAL COMPONENTS OF NEUROENDOCRINE PATHWAYS AND AUTONOMIC NERVOUS SYSTEM (ANS) FUNCTIONING WHICH, IN TURN, INFLUENCE THE IMMUNE SYSTEM. STARTING IN UTERO, ENVIRONMENTAL FACTORS, INCLUDING AIR POLLUTANTS, MAY PERMANENTLY ORGANIZE THESE SYSTEMS TOWARD TRAJECTORIES OF ENHANCED PEDIATRIC (E.G., ASTHMA, ALLERGY) AS WELL AS ADULT DISEASE RISK (E.G., CHRONIC OBSTRUCTIVE PULMONARY DISEASE). EVIDENCE SUPPORTS A CENTRAL ROLE OF OXIDATIVE STRESS IN THE TOXIC EFFECTS OF AIR POLLUTION. ADDITIONAL RESEARCH SUGGESTS XENOBIOTIC METABOLISM AND SUBCELLULAR COMPONENTS, SUCH AS MITOCHONDRIA ARE TARGETS OF AMBIENT AIR POLLUTION AND PLAY A ROLE IN ASTHMA AND ALLERGY PROGRAMMING. MECHANISMS OPERATING AT THE LEVEL OF THE PLACENTA ARE BEING ELUCIDATED. EPIGENETIC MECHANISMS MAY BE AT THE ROOTS OF ADAPTIVE DEVELOPMENTAL PROGRAMMING. SUMMARY: OPTIMAL COORDINATED FUNCTIONING OF MANY COMPLEX PROCESSES AND THEIR NETWORKS OF INTERACTION ARE NECESSARY FOR NORMAL LUNG DEVELOPMENT AND THE MAINTENANCE OF RESPIRATORY HEALTH. OUTDOOR AIR POLLUTION MAY PLAY AN IMPORTANT ROLE IN EARLY PROGRAMMING OF RESPIRATORY HEALTH AND IS POTENTIALLY AMENABLE TO INTERVENTION. 2013 15 754 36 CARDIOVASCULAR ADAPTATIONS TO PARTICLE INHALATION EXPOSURE: MOLECULAR MECHANISMS OF THE TOXICOLOGY. AMBIENT AIR, OCCUPATIONAL SETTINGS, AND THE USE AND DISTRIBUTION OF CONSUMER PRODUCTS ALL SERVE AS CONDUITS FOR TOXICANT EXPOSURE THROUGH INHALATION. WHILE THE PULMONARY SYSTEM REMAINS A PRIMARY TARGET FOLLOWING INHALATION EXPOSURE, CARDIOVASCULAR IMPLICATIONS ARE EXCEPTIONALLY CULPABLE FOR INCREASED MORBIDITY AND MORTALITY. THE EPIDEMIOLOGICAL EVIDENCE FOR CARDIOVASCULAR DYSFUNCTION RESULTING FROM ACUTE OR CHRONIC INHALATION EXPOSURE TO PARTICULATE MATTER HAS BEEN WELL DOCUMENTED, BUT THE MECHANISMS DRIVING THE RESULTING DISTURBANCES REMAIN ELUSIVE. IN THE CURRENT REVIEW, WE AIM TO SUMMARIZE THE CELLULAR AND MOLECULAR MECHANISMS THAT ARE DIRECTLY LINKED TO CARDIOVASCULAR HEALTH FOLLOWING EXPOSURE TO A VARIETY OF INHALED TOXICANTS. THE PURPOSE OF THIS REVIEW IS TO PROVIDE A COMPREHENSIVE OVERVIEW OF THE BIOCHEMICAL CHANGES IN THE CARDIOVASCULAR SYSTEM FOLLOWING PARTICLE INHALATION EXPOSURE AND TO HIGHLIGHT POTENTIAL BIOMARKERS THAT EXIST ACROSS MULTIPLE EXPOSURE PARADIGMS. WE ATTEMPT TO INTEGRATE THESE MOLECULAR SIGNATURES IN AN EFFORT TO PROVIDE DIRECTION FOR FUTURE INVESTIGATIONS. THIS REVIEW ALSO CHARACTERIZES HOW MOLECULAR RESPONSES ARE MODIFIED IN AT-RISK POPULATIONS, SPECIFICALLY THE IMPACT OF ENVIRONMENTAL EXPOSURE DURING CRITICAL WINDOWS OF DEVELOPMENT. MATERNAL EXPOSURE TO PARTICULATE MATTER DURING GESTATION CAN LEAD TO FETAL EPIGENETIC REPROGRAMMING, RESULTING IN LONG-TERM DEFICITS TO THE CARDIOVASCULAR SYSTEM. IN BOTH DIRECT AND INDIRECT (GESTATIONAL) EXPOSURES, CONNECTING THE BIOCHEMICAL MECHANISMS WITH FUNCTIONAL DEFICITS OUTLINES PATHWAYS THAT CAN BE TARGETED FOR FUTURE THERAPEUTIC INTERVENTION. ULTIMATELY, FUTURE INVESTIGATIONS INTEGRATING "OMICS"-BASED APPROACHES WILL BETTER ELUCIDATE THE MECHANISMS THAT ARE ALTERED BY XENOBIOTIC INHALATION EXPOSURE, IDENTIFY BIOMARKERS, AND GUIDE IN CLINICAL DECISION MAKING. 2020 16 4881 31 OVERVIEW OF THE CARDIOVASCULAR EFFECTS OF ENVIRONMENTAL METALS: NEW PRECLINICAL AND CLINICAL INSIGHTS. ENVIRONMENTAL CAUSES OF CARDIOVASCULAR DISEASES (CVDS) ARE GLOBAL HEALTH ISSUES. IN PARTICULAR, AN ASSOCIATION BETWEEN METAL EXPOSURE AND CVDS HAS BECOME EVIDENT BUT CAUSAL EVIDENCE STILL LACKS. THEREFORE, THIS SYMPOSIUM AT THE SOCIETY OF TOXICOLOGY 2022 ANNUAL MEETING ADDRESSED EPIDEMIOLOGICAL, CLINICAL, PRE-CLINICAL ANIMAL MODEL-DERIVED AND MECHANISM-BASED EVIDENCE BY FIVE PRESENTATIONS: 1) AN EPIDEMIOLOGIC STUDY ON POTENTIAL CVD RISKS OF INDIVIDUALS EXPOSED OCCUPATIONALLY AND ENVIRONMENTALLY TO HEAVY METALS; 2) BOTH PRESENTATIONS OF THE SECOND AND THIRD WERE CLINICAL STUDIES FOCUSING ON THE POTENTIAL LINK BETWEEN HEAVY METALS AND PULMONARY ARTERIAL HYPERTENSION (PAH), BY PRESENTING ALTERED BLOOD METAL CONCENTRATIONS OF BOTH NON-ESSENTIAL AND ESSENTIAL METALS IN THE PATIENTS WITH PAH AND POTENTIAL THERAPEUTIC APPROACHES; 3) ARSENIC-INDUCED ATHEROSCLEROSIS VIA INFLAMMATORY CELLS IN MOUSE MODEL; 4) PATHOGENIC EFFECTS ON THE HEART BY ADULT CHRONIC EXPOSURE TO VERY LOW-DOSE CADMIUM VIA EPIGENETIC MECHANISMS AND WHOLE LIFE EXPOSURE TO LOW DOSE CADMIUM VIA EXACERBATING HIGH-FAT-DIET-LIPOTOXICITY. THIS SYMPOSIUM HAS BROUGHT EPIDEMIOLOGISTS, THERAPEUTIC INDUSTRY, PHYSICIANS, AND TRANSLATIONAL SCIENTISTS TOGETHER TO DISCUSS THE HEALTH RISKS OF OCCUPATIONAL AND ENVIRONMENTAL EXPOSURE TO HEAVY METALS THROUGH DIRECT CARDIOTOXICITY AND INDIRECT DISRUPTION OF HOMEOSTATIC MECHANISMS REGULATING ESSENTIAL METALS, AS WELL AS LIPID LEVELS. THE DATA SUMMARIZED BY THE PRESENTERS INFERS A POTENTIAL CAUSAL LINK BETWEEN MULTIPLE METALS AND CVDS AND DEFINES DIFFERENCES AND COMMONALITIES. THEREFORE, SUMMARY OF THESE PRESENTATIONS MAY ACCELERATE THE DEVELOPMENT OF EFFICIENT PREVENTIVE AND THERAPEUTIC STRATEGIES BY FACILITATING COLLABORATIONS AMONG MULTIDISCIPLINARY INVESTIGATORS. 2022 17 6833 28 [HYPOTHETICAL LINK BETWEEN ENDOMETRIOSIS AND XENOBIOTICS-ASSOCIATED GENETICALLY MODIFIED FOOD]. ENDOMETRIOSIS IS AN OESTROGEN-DEPENDENT INFLAMMATORY DISEASE AFFECTING 10 % OF REPRODUCTIVE-AGED WOMEN. OFTEN ACCOMPANIED BY CHRONIC PELVIC PAIN AND INFERTILITY, ENDOMETRIOSIS RIGOROUSLY INTERFERES WITH WOMEN'S QUALITY OF LIFE. ALTHOUGH THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS REMAINS UNCLEAR, A GROWING BODY OF EVIDENCE POINTS TO THE IMPLICATION OF ENVIRONMENTAL TOXICANTS. OVER THE LAST DECADE, AN INCREASE IN THE INCIDENCE OF ENDOMETRIOSIS HAS BEEN REPORTED AND COINCIDES WITH THE INTRODUCTION OF GENETICALLY MODIFIED FOODS IN OUR DIET. EVEN THOUGH ASSESSMENTS OF GENETICALLY MODIFIED FOOD RISK HAVE NOT INDICATED ANY HAZARD ON HUMAN HEALTH, XENOBIOTICS-ASSOCIATED GENETICALLY MODIFIED FOOD, SUCH AS PESTICIDES RESIDUES AND XENOPROTEINS, COULD BE HARMFUL IN THE LONG-TERM. THE "LOW-DOSE HYPOTHESIS", ACCUMULATION AND BIOTRANSFORMATION OF PESTICIDES-ASSOCIATED GENETICALLY MODIFIED FOOD AND THE MULTIPLIED TOXICITY OF PESTICIDES-FORMULATION ADJUVANTS SUPPORT THIS HYPOTHESIS. THIS REVIEW SUMMARIZES TOXIC EFFECTS (IN VITRO AND ON ANIMAL MODELS) OF SOME XENOBIOTICS-ASSOCIATED GENETICALLY MODIFIED FOOD, SUCH AS GLYPHOSATE AND CRY1AB PROTEIN, AND EXTRAPOLATES ON THEIR POTENTIAL ROLE IN THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS. THEIR ROLES AS IMMUNE TOXICANTS, PRO-OXIDANTS, ENDOCRINE DISRUPTORS AND EPIGENETIC MODULATORS ARE DISCUSSED. 2010 18 299 37 AIR POLLUTION AND DNA METHYLATION: EFFECTS OF EXPOSURE IN HUMANS. AIR POLLUTION EXPOSURE IS ESTIMATED TO CONTRIBUTE TO APPROXIMATELY SEVEN MILLION EARLY DEATHS EVERY YEAR WORLDWIDE AND MORE THAN 3% OF DISABILITY-ADJUSTED LIFE YEARS LOST. AIR POLLUTION HAS NUMEROUS HARMFUL EFFECTS ON HEALTH AND CONTRIBUTES TO THE DEVELOPMENT AND MORBIDITY OF CARDIOVASCULAR DISEASE, METABOLIC DISORDERS, AND A NUMBER OF LUNG PATHOLOGIES, INCLUDING ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). EMERGING DATA INDICATE THAT AIR POLLUTION EXPOSURE MODULATES THE EPIGENETIC MARK, DNA METHYLATION (DNAM), AND THAT THESE CHANGES MIGHT IN TURN INFLUENCE INFLAMMATION, DISEASE DEVELOPMENT, AND EXACERBATION RISK. SEVERAL TRAFFIC-RELATED AIR POLLUTION (TRAP) COMPONENTS, INCLUDING PARTICULATE MATTER (PM), BLACK CARBON (BC), OZONE (O(3)), NITROGEN OXIDES (NO(X)), AND POLYAROMATIC HYDROCARBONS (PAHS), HAVE BEEN ASSOCIATED WITH CHANGES IN DNAM; TYPICALLY LOWERING DNAM AFTER EXPOSURE. EFFECTS OF AIR POLLUTION ON DNAM HAVE BEEN OBSERVED ACROSS THE HUMAN LIFESPAN, BUT IT IS NOT YET CLEAR WHETHER EARLY LIFE DEVELOPMENTAL SENSITIVITY OR THE ACCUMULATION OF EXPOSURES HAVE THE MOST SIGNIFICANT EFFECTS ON HEALTH. AIR POLLUTION EXPOSURE-ASSOCIATED DNAM PATTERNS ARE OFTEN CORRELATED WITH LONG-TERM NEGATIVE RESPIRATORY HEALTH OUTCOMES, INCLUDING THE DEVELOPMENT OF LUNG DISEASES, A FOCUS IN THIS REVIEW. RECENTLY, INTERVENTIONS SUCH AS EXERCISE AND B VITAMINS HAVE BEEN PROPOSED TO REDUCE THE IMPACT OF AIR POLLUTION ON DNAM AND HEALTH. ULTIMATELY, IMPROVED KNOWLEDGE OF HOW EXPOSURE-INDUCED CHANGE IN DNAM IMPACTS HEALTH, BOTH ACUTELY AND CHRONICALLY, MAY ENABLE PREVENTATIVE AND REMEDIAL STRATEGIES TO REDUCE MORBIDITY IN POLLUTED ENVIRONMENTS. 2019 19 1916 42 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 20 4541 47 MULTISYSTEMIC ALTERATIONS IN HUMANS INDUCED BY BISPHENOL A AND PHTHALATES: EXPERIMENTAL, EPIDEMIOLOGICAL AND CLINICAL STUDIES REVEAL THE NEED TO CHANGE HEALTH POLICIES. A VAST AMOUNT OF EVIDENCE INDICATES THAT BISPHENOL A (BPA) AND PHTHALATES ARE WIDELY DISTRIBUTED IN THE ENVIRONMENT SINCE THESE COMPOUNDS ARE MASS-PRODUCED FOR THE MANUFACTURE OF PLASTICS AND PLASTICIZERS. THESE COMPOUNDS BELONG TO A LARGE GROUP OF SUBSTANCES TERMED ENDOCRINE-DISRUPTING CHEMICALS (EDC). IT IS WELL KNOWN THAT HUMANS AND LIVING ORGANISMS ARE UNAVOIDABLY AND UNINTENTIONALLY EXPOSED TO BPA AND PHTHALATES FROM FOOD PACKAGING MATERIALS AND MANY OTHER EVERYDAY PRODUCTS. BPA AND PHTHALATES EXERT THEIR EFFECT BY INTERFERING WITH HORMONE SYNTHESIS, BIOAVAILABILITY, AND ACTION, THEREBY ALTERING CELLULAR PROLIFERATION AND DIFFERENTIATION, TISSUE DEVELOPMENT, AND THE REGULATION OF SEVERAL PHYSIOLOGICAL PROCESSES. IN FACT, THESE EDC CAN ALTER FETAL PROGRAMMING AT AN EPIGENETIC LEVEL, WHICH CAN BE TRANSGENERATIONAL TRANSMITTED AND MAY BE INVOLVED IN THE DEVELOPMENT OF VARIOUS CHRONIC PATHOLOGIES LATER IN THE ADULTHOOD, INCLUDING METABOLIC, REPRODUCTIVE AND DEGENERATIVE DISEASES, AND CERTAIN TYPES OF CANCER. IN THIS REVIEW, WE DESCRIBE THE MOST RECENT PROPOSED MECHANISMS OF ACTION OF THESE EDC AND OFFER A COMPELLING SELECTION OF EXPERIMENTAL, EPIDEMIOLOGICAL AND CLINICAL STUDIES, WHICH SHOW EVIDENCE OF HOW EXPOSURE TO THESE POLLUTANTS AFFECTS OUR HEALTH DURING DEVELOPMENT, AND THEIR ASSOCIATION WITH A WIDE RANGE OF REPRODUCTIVE, METABOLIC AND NEUROLOGICAL DISEASES, AS WELL AS HORMONE-RELATED CANCERS. WE STRESS THE IMPORTANCE OF CONCERN IN THE GENERAL POPULATION AND THE URGENT NEED FOR THE MEDICAL HEALTH CARE SYSTEM TO CLOSELY MONITOR EDC LEVELS IN THE POPULATION DUE TO UNAVOIDABLE AND INVOLUNTARY EXPOSURE TO THESE POLLUTANTS AND THEIR IMPACT ON HUMAN HEALTH. 2021