Environmental justice, global issues, e-waste, exposure dose response, metabolism and susceptibility and environmental basis of cancer
Environmental justice, global issues, e-waste, exposure dose response, metabolism and susceptibility and environmental basis of cancer PUH 210
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This 17 page Test Prep (MCAT, SAT...) was uploaded by Isis Dana Kanakri on Monday September 21, 2015. The Test Prep (MCAT, SAT...) belongs to PUH 210 at University of Alabama at Birmingham taught by Dale A Dickinson (P) in Fall 2015. Since its upload, it has received 192 views. For similar materials see Public Health Biological Basis in Public Health at University of Alabama at Birmingham.
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Date Created: 09/21/15
Lecture 2 What is the singlemost fundamental component of public health The study of the interactions of people with their environments What diminishes health in some areas Lack of public health promotion and education significantly diminishes health in some areas Ancient humans protection from the elements Ancient humans lived in natural caves and rock shelters and crude manmade shelters to protect themselves from their natural elements today elements can be harsh and have profound impacts on our health Branches reeds leantos temporary shelters enabled native people to move frequently from one place to another as resources cactus fruits nuts deer depleted They also used stones rocks and other materials Researchers proved by sample testing mummies lungs that there were high levels of smoke in the cave and indoor air pollution was equal to that of a modern developed country example of history repeats itself Egyptians got permission to take out lung sample from old corpse most of past air pollution was from wood burning All components of air pollution causes lung diseases Today women doing cooking indoors without ventilation caused premature deaths biomass wood plastic dry feces being burned Ancient humans issues 1 removal of contaminated water was a public health issue Aqueduct for clean water and ancient sewage system to remove waste India Rome Greece Egypt South America from 2000BC gt Aquadox Industrial revolution cities grew faster than water came in disease spread by no ventilation littering inadequate nonexistent water systems human wastes on unpaved roads over crowdedness Raw sewage dumped into open sewers in Sheffield caused a cholera epidemic 2 food preservation became important to prevent food borne illness Drying smoking or salting became common methods to preserve meat methods known to increase cancers and cardiovascular diseases dietary laws in effect some foods banned like Islam Jews pigs Leprous disease Biblical text reference MoldMildew If contamination existed they had to remove the entire structure as hazardous waste and dump it outside the city De ne Environment All that which is external to the individual host Physical biological social and cultural any of all of which can in uence health status in populations Environment classi cations G1 vs Skin 3 barriers to inner body 1 Skin 2 GI tract 3 Lungs poses the highest threat hygiene control vs working environment little control the three states of matter determine exposure to contaminants Useful to consider how pollution occurred and what measures to take and how to avoid exposure Gas air Liquid water Solid Landlandfills Biological diseasecausing organisms in food water Chemical toxic waste preservatives pesticides Physical Injuries deaths from accidentsnoiseheatcold Socioeconomic statistical relationship between morbiditymortality and people s lifestyles Ex job availability neighborhood violence inadequate nutrition etc Nongenetic factors 1 Physical 2 Nutritional 3 Social 4 Behavioral 5 Economic others that act on humans De ne Health A state of complete physical mental and social wellbeing and not merely the absence of disease or infirmity WHO 1948 De ne Environmental Health Environmental health is the discipline that focuses on the interrelationships between people and their environment promotes human health and wellbeing and fosters a safe and healthful environment NCEH 1998 What is the mission of NIEHS NIEHS National Institutes of Environmental Health Sciences The mission of NIEHS is to reduce the burden of human illness and disability by understanding how the environment in uences the development and progression of human disease Things to remember Tobacco smoking is the single largest cause of preventable death in the US Air pollution does NOT only affect the lungs Genetics is not an acquired factor wit vulnerable populations Proximity to a pollution source is not the same thing as exposure The executive order 12898 signed by president Clinton 1994 achieved in regulating a law that serves environmental justice towards minority populations and lowincome populations Some jobs you can get in environmental health is environmental health inspector food safety inspector toxicologist industrial hygienist Central Park in New York City was originally created as a public health effort to create a park where people can go where there is clean air Lecture 4 Environmental Justice represents the convergence of two of the greatest social movements of the latter half of the 20th century 1982 birth of environmental justice movement 1 The civil rights movement 2 The environmental movement What was perhaps the worst occupational health disaster in the US Gauley Creek West Virginia during the Great Depression of the 1930s 500 African Americans workers died and more than 1500 were disabled due to Silicosis lung disease that takes years to develop while digging a tunnel for the New Kanawha Power Company They were earning 25 30 centshr had no masks or venting while supervisors had masks their sickness developed in months instead of years because of very dense dust and then buried in 2 s or 3 s per unmarked grave What happened in Warren County North Carolina in 1982 What did it give rise to Blacks and Whites in Warren County united to stop the siting of a PCB landfill They lay on the ground in front of trucks This was not successful PCBs dumped anyway people lived there 25 years and issue still being fought 30 years later It did however bring together the environmental and civil rights communities and attracted national attention It gave rise to the landmark 1987 United Church of Christ UCC study Toxic wastes and race in the United States the first national study of the demographic patterns associated with the location of hazardous waste sites Define Environmental Racism The tendency of toxic waste sites and emitters to be located near communities of color it had nothing to do with wealthy or poor just race What did White communities see compared to Blacks Hispanics and where other minorities lived 1 Faster action 2 Better results 3 Stiffer penalties The minorities called for a change in these disparities Disproportionate impacts refer to inequities in levels of 1 Harmful environmental exposures 2 Deficient services or benefits 3 Diminished ability to withstand or mitigate harms 4 Or any combination of these Contributorscomponents toof disproportionate impacts 1 waste sites industrial facilities racial minority 2 ater contamination population fishing eat fish get sick African Americans near Detroit MI Asians around Seattle WA red tides toxic shellfish 3 Intrinsic factors related to susceptibility age sex genetics race ethnicity Acquired factors chronic medical conditions health care access nutrition fitness other pollutant exposures drug and alcohol use and lack of political power 4 exposed to multiple different individual effects cumulative effects disadvantaged cigarette smoking vehicle exhaust must consider additive synergy for cumulative risk 5 vulnerable populations recognizes employment status access to health insurance language ability access to social capital these all play a role in determining the response to environmental insult social problems limit meaningful involvement in environmental decision making process Risk equation the magnitude and severity of exposures the nature of the receptor population biological and social aspects of vulnerability must be taken into account LULU Locally undesirable land use Vulnerability to harmful effects on health determined by 1 Susceptibility 2 Exposure 3 Preparedness 4 And ability to respond and recover focus on just population and prevention is narrow Executive Order 12898 protected groups President Clinton signed February 11 1994 Federal actions to address environmental justice in minority populations and lowincome populations The order created no new rights or obligations but it helped overlooked situations When trying to achieve environmental justice and healthy communities you must do collaborative problem solving create community benefits agreements build strategic thinking planning and problem solving capacity of communities and engage in community based participatory research Social capital helps determine social determinants of health39 income distribution discrimination access to education and housing policies Lecture 5 One Earth three worlds First world Second world Third world Developed countries Highincome developing Lowincome developing countries countries Developed economies Developing economies Underdeveloped economies upper earth middle earth lower earth Postmodem hazards Modern hazards accidents Traditional hazards diseases pollution starvation Sedentary lifestyles and Uncontrolled industrial Generally associated with material excess development lack of development 60 death over age 70 10 death over 70 rest among younger age I I population I Risk transitions and risk overlap occur as developing nations move from one stage into the next Risk overlap can be severe from 3rd2rld stage world transitioning due to poor living new pollution Define Environmental Drivers Factors that stimulate motivate or push the environmental processes that affect human health population growth technological economic development policy interventions natural processes of change in the physical environment etc contributes directly and indirectly to health disparities among the three worlds Four common Environmental Drivers The vulnerability of any human population to external stresses is a function of a Exposure b Sensitivity c Adaptive capacity Two main elements of human vulnerability are a Exposure to environmental hazards stressors shocks contingencies b Coping capacity resilience which can offer security in the face of exposure Environmental vulnerabilitysecurity continuum a High risk high coping capacity USA b High risk low coping capacity third world creates environmental refugees seeking refuge in hazardous biophysical environments c Low risk low coping capacity d Low risk high coping capacity IDEAL SCENARIO 2 process of interlocking economic social technological political and cultural changes emerging around the world As economies grow 1st world gets richer some in 2rld world escape poverty and 3rd world disparities widen Wealth and health in 1st world are increasingly being created at the cost of development in the other 2 worlds Despite advances morbidity and mortality experienced in 1St and 3rd worlds What are the ill effects of poverty a Clean water and proper sanitation b Migration into overcrowded cities with bad air and poor housing c Exposure to lead indoor air pollution biofuels and solid wastes 3 due to social political and economic constraints and lack of education under nutrition remains a leading risk factor for ill health and premature death in most 3rd world countries yet there is no global food shortage nor the capacity to produce more food Subsistence agriculture does not provide adequately for 3rd world countries which is why there is a need for the integration of modern techniques of food production to allow the feeding of the population and the growth of cash crops for the export market Environmental factors water availability physical chemical properties of soil prevailing climatic conditions control local food pattern and determine the bioavailable forms of essential microelements in soils and hence their concentrations in food Foods in developing countries naturally less microelements in comparison Zn Cu Co and Se lack in red soils Se deficiency in China Factors that in uence under nutrition a Traditional beliefs that limit food choice b Reduced capacity for local food production c Declining investments in agriculture and irrigation d Lack of education on advanced technologies e Destruction of local ecosystems forestsfarms f Lack of adequate food storage and distribution Urbanicity the extent of urban population concentration Urbanization the process over time or urban growth Wealthy countries Developing countries Under developed countries High urbanicity Rapid urbanization causes outstrip of resources good factor predictor of health Urban areas rapid growth leads to a Migration to urban areas b Natural increase in population excess births over deaths High rate of urban growth increase in demand for housing and services distribution of investment towards suburban developments rapid expansion of illegal unplanned unserviced settlements with unhealthy living conditions extreme overcrowding growth of slums Physical environment stressors a Chemical biological agents b Natural disasters c Noise pollution d Extreme heat Urban health in developing nations a Ambient air pollution caused by industrial and transportationrelated sources and combustion byproducts from domestic cooking and heating b Indoor air quality pollution from dirtyburning fuels from cooking c Water may contaminate supplies d Infectious disease high population density crowded conditions concentration of commerce increase the probability transmission leading to the emergence and reemergence of infectious diseases e Waste disposal polluting industries waste dumps waste management facilities near low income neighborhoods cause pollution and exposure Contaminated water supplies and human wastes can go to the local food chain and cause illness f Disaster vulnerability many cities in developing nations live close to the coast and are vulnerable to sealevel rise extreme weather events and ooding Poor quality of construction in many urban areas cause an increase to damage during natural disasters g Social and behavioral factors increasing urbanization increase in sexual activity participation lower quality diet insufficient access to adequate health care and few legal rights Health disparities across three worlds 1 causes chronicacute health effects In 1st world decreasing In 2rld world increasing 3rd world biomass fuels for energy and no ventilation causing incomplete combustion and harmful air pollutants Water 900 million people in developing countries live without continuous access to safe drinking water In lowincome developing countries 50 has access to safe drinking water compared to 7590 in highincome developing countries and 90 in developed countries Lowincome developing countries on the rural side have considerably less access to safe drinking water compared to those living in urban populations Sanitation 62 of the world has access to improved sanitation facilities Without caring for water it can spread communicable disease Safe water systems to reduce contaminants are efforts made in third world 3 intentional and unintentional All injuries are preventable Intentional rape battery child abuse suicide Unintentional road traffic injuries fires drowning falls natural disaster hidden epidemic among young adults in developing countries Examples of environmental factors that drive injuries a Poorly designed cook stoves b Poorly designed roadways c Substandard housing at risk of collapse Lecture 6 EWaste What are some environmental factors that negatively impact ewaste recyclers in under developed nations 1 Exposure to air pollution 2 Exposure to ground water 3 Exposure to fresh fruit markets being pollution by the burning of ewastes causing lung problems headaches malnourishment 4 Exposure to acid baths to get gold out of computer boards In what ways would you describe the ecyclers in under developed nations as being vulnerable They are being exposed to toxins in order to make money for their livelihood because they re poor and because they re poor they have a low coping capacity How does ewaste illustrate 1 It s an environmental justice issue because environmental justice is the fair treatment among populations regardless their race color natural origin income or economic development among other things However in Africa they are not being treated fair because developed nations are sending their ewaste to the under developed nations without consent without their involvement and it is affecting the health of the populations It is a global justice issue because the populations of the world should at least have a say in what goes into the country in which they reside However the powerful wealthier nations are taking advantage of 3rd world nations because of their lack of political power and legal rights The people of the 3rd world do not have a voice and the wealthy are dumping hazardous toxic wastes into their country and get away with it by calling the wastes charitable goods What does the 1989 Basel convention do The 1989 Basel Convention bans exports of hazardous waste from rich to poor nations USA s the only developed country that hasn t taken responsibility for its own mess by ratifying the treaty Lecture 7 De ne Toxicology the study of the adverse effects of chemicals on biological systems mechanistically based science incorporates genetic variability Applied to make safety evaluations and management decisions Protect human health from environmental and occupational diseases from exposures examples green toxicology molecular toxicology Poison any agent capable of producing a deleterious response in a biological system Paracelsus one of the founders of modern toxicology the dose makes the poison Frenchwoman direct forensic toxicological evidence Toxicity the degree to which something is poisonous Toxicant Toxic substances that are manmade Toxin Toxic substances made by living organisms Xenobiotic a chemical foreign to the body Exposure refers to any condition which provides an opportunity for an external environmental agent to enter the body Dose refers to the amount of agent actually deposited within the body Response refers to the biological effect s of the agent Latency the time period between initial exposure and a measurable response few seconds decades Subjects used to test chemicals 1 Volunteers who have had normal or accidental exposures 2 Animals exposed purposively 3 Cells derived from human animal or plant sources Routes of exposure to toxins the route affects the toxicity of agents 1 Dermal exposure through the skin 2 Ingestion GI system from eating and drinking 3 Inhalation through the lungs Types of duration exposures Acute usually a single exposure for less than 24 hours Subacute exposure for one month or less Chronic exposure for more than three months Subchronic exposure for one to three months PP P 2 examples of dose descriptions 1 Absorbed dose internal dose 2 Exposure dose external dose 3 Biologically effective dose LD50 lethal dose death 50 of exposed animals dosage mgkg in body weight Low LD50 more poisonous Location of the response 1 Local effects damage at the site Where a chemical first comes into contact With the body 2 Systemic effects generalized distribution of the chemical throughout the body by the blood stream to internal organs 3 Target organ effects some chemicals may confine their effects to specific organs Health effects Responses classes Adverse vs beneficial carcinogen vs anticarcinogen Acute vs delayed onset asthmas vs emphysema Clinical vs subclinical manifestations cluster migraines vs headaches Transient reversible vs chronic irreversible shortness of breath vs Parkinson s disease PP N Doseresponse relationship the characteristics of an exposure to a chemical and the spectrum of effects caused by the chemical When evaluating a doseresponse relationship 1 It must be known that the response observed is due to the exposure to the compound 2 The magnitude of the response should be a function of the dose administered 3 There should be a quantitative method for measuring the response Doseresponse curves 1 Individual 2 Population Chemical mixtures effects 4 examples definition 1 Additive the combination of two chemicals produces an effect that is equal to their individual effects added together 224 2 Synergism the combined effect of exposures to two or more chemicals is greater than the sum of their individual effects 22gt4 3 Potentiation one chemical that is not toxic causes another chemical to become more toxic 03gt3 4 Antagonism two chemicals administered together interfere with each other s actions or one interferes with the action of the other 45lt9 Lecture 8 De ne Absorption the passage of substances across the membranes through some body surfaces into body uids and tissues through diffusion active transportation etc For a systemic effect a toxicant has to be internal defeat barriers to absorption otherwise all effects are confined to the site like a local toxicity irritation to skin or respiratory tract An orally consumed or inhaled toxicant respiratory system is not considered internal until it moves across the epithelial cellular membranes getting into internal uid compartments of body Absorption passages 1 Dermal 2 Ingestion 3 Inhalation a Respiratory absorption Important route of exposure for airborne contaminants toxic gases particulates etc Toxicants that are inhaled are absorbed through 3 pathways nasopharyngeal tracheobronchial pulmonary exchange surfaces of the lungs depending on physical chemical properties of the toxicant b Gastrointestinal absorption depends on site time and physicochemical properties of the chemical Chemicals entering the GI tract must first cross mucosa somewhere along the track before gaining entry into the blood it takes for a chemical to exert a toxic effect that could be considered systemic Toxicant absorption in the upper GI tract less toxicity compared to lower part stomach and GI tract the chemicals go through your liver before it is circulated throughout your blood they cannot escape hepatic metabolism c Skin absorption Outer layer of skin stratum corneum is the first line of defense between dermal exposure and systemic toxicity Damage to the integrity of the skin increases absorption and may lead to greater systemic toxicity Lipophilic chemicals in nature get inside our skin better than aqueous solutions and ions Define Distribution the process in Which a chemical agent after first gaining entry into the internal body uid usually the blood translocates moves travels throughout the uid compartments of the body The blood carries the toxicant to its sites of action storage and elimination Distribution of a toxicant factors 1 Lipid solubility 2 Ease of crossing cell membranes 3 Blood ow to the tissue or organs Storage occurs mostly in connective tissues fat and bone bone osseous tissue good storage place for lead strontium and uoride also commonly in livi and kidneys relatively high blood ow may store toxicants in amounts greater than other organs Despite the process of the mobilization of elements out of the bone like When there needs to be bone remodelling it has relatively low blood supply and metals that are in bones could stay in there for decades Adipose tissue located in many parts of body accumulated in subcutaneous tissue Where lipophilic toxicants are stored and mobilized back into blood for further distribution metabolism elimination and redeposition Toxicant elimination lead to a decrease in the amount of toxicant 1 in uenced by factors that are related to the properties of the toxicant a Molecular size easily filtered if not protein bound b Water solubility ionized toxicants are ready to eliminate lipophilic toxicants reenter into the renal circulation so they stay longer bilary excretion is the main route of GI elimination of toxicants and their metabolites This slow elimination pathway is mostly important When the urinary or biliary excretion have become less effective GI tract exists a Through their direct discharge into the lumen of the GI tract b Through excretion in bile elimination by simple diffusion volatile liquid and gases route Important factors that determine elimination of chemicals from the lungs a Concentration differences between alveolar air and blood plasma b Vapor pressure c Plasma solubility Lecture 9 Define Metabolism can be any change that occurs to a compound once inside the body Define Biotransformation is the sum of all chemical processes of the body that modify a compound between absorption and excretion Define Enzymes are biological catalysts that allow for biotransformation reactions to proceed at rates that are consistent with life Enzymes are proteins and proteins are encoded by genes Therefore due to the gene variants alleles some people have different behaving enzymes moreless active and explains why some peoplepopulations display susceptibilityresistance If one enzyme works faster while the other works slower it makes us sick Many enzymes a large number are required to allow the biotransformation of toxicants and the resulting modified product of the parent compound is the product called a metabolite Metabolites are also used by the body to improve or impede physiological function elimination or storage Biotransformation s wisdom is to detoxify chemicals 0 Render them LESS harmful through enzymatic modifications 0 Render them MORE water soluble to facilitate elimination from the body Bioactivation is when biotransformation results in the production of a metabolite that is MORE toxic than the parent compound Different enzymes of the body may compete for the same toxicant producing different metabolites that may greatly vary in their toxicity For example mutation or loss of activity of the P450 would make the person MORE susceptible to anilinebased toxicity bioactivation while the mutation or loss of activity of the NHydroxylase would make the person LESS susceptible to anilinebased toxicity biotransformation Identical exposure can still exhibit great differences in the response of individuals because each person is genetically and environmentally unique Enzymes for biotransformation are found in tissues where biotransformation occurs 0 Liver highest capacity because of its high concentration of enzymes 0 Lungs Kidneys 15 a fifth of the liver s biotransformation capacity Reactions can be categorized by type the nature of the chemical modification or order which reactions proceed others Phase 1 2 Phase 1 Phase 2 Oxidation Sulfate conjugation Reduction Glucuronide conjugation Hydrolysis Glutathione conjugation Acetylation Amino acid conjugation Phase 1 Phase 2 Where bioactivation would occur usually detoxifying almost never bioactivates Simple unmasking polar groups addition of polar groups to molecule eg hydroxyl OH Conjugation reactions physical joining together molecule present just attaches itself to the reactive site of Phase 1 metabolite Increases solubility Usually carried by cytochrome P450 enzymes CYPs a large class of enzymes With various degrees of specificity More water soluble than phase 1 metabolite and can be readily eliminated from the body May be more effective and in many of those cases more toxic than parent compound Reactions usually detoxifying the product of the phase 2 reaction is less toxic than the metabolite Phase 1 doesn t always come first sometimes both phases are phase 2 hopefully one is detoxifying Factors affecting biotransformation toxicant host Host factors 0 Age 0 Sex 0 Nutritional status 0 Existing disease 0 Enzyme induction 0 Genetic variability toxicogenetics 0 Cultural practices 0 Exposure history 0 Behavior choices smoking Also recall the increased susceptibility if the mutation or loss of P450 for example Example drug Isoniazid for tuberculosis Slow acetylators possess a mutation or enzyme that is less effective 3 hours to eliminate half the dose greater risk for developing isoniazid toxicity Fast acetylators possess normal form of enzyme 1 hour to eliminate half the dose Latency affects Exposure internal dose biologically effective dose early biologic effects altered structure and function clinical disease are altered by 0 Susceptibility genetic factors 0 Effect modifiers diet habits health medication coexposure Pharmacogenomics toxicogenomics offers the potential to identify and protect subsets of people predisposed to toxicity from chemicalsdrugs Acetaminophen is dangerous when taken so much of bad for the liver 95 of metabolites formed during pharmacologically relevant exposures large doses taken too frequently can overwhelm the conjugating enzymes and result in toxicity Lecture 10 Environment causes 7080 diseases and 8090 cancer Components from the environment 0 Occupational Exposures high concentrations of 0 Lifestyle factors tobacco obesity inactivity 0 HomeCommunity low chronic exposures Evidence for it being environmental 0 groups with higher exposure to chemicals than most population Asbestos Mesothelioma Benzidine textile paper and leather products Bladder cancer 1921 Benzoapyrene Skin cancer 1930s 0 people who take on cancer rates of the country to which they move It is the environment that determines cancer risk not hereditary genetic prostate and breast increase moving east to west stomach cancer decreases moving east to west 0 out of 90000 twins only 10 reported to have the same cancer Prostate cancer has high heritability uterine and cervical show low heritability 0 changes in cancer incidence some time after the startcessation of an exposure IARC International Agency for Research on Cancer agents are selected for review based on two main criteria 0 Evidence of human exposure 0 Some evidencesuspicion of carcinogenicity The agentmixture is 0 Group 1 Carcinogenic to humans 117 Yes sufficient evidence 0 Group 2A Probably carcinogenic to humans 74 Good chance limited evidence 0 Group 2B Possibly carcinogenic to humans 287 Maybe limited evidence 0 Group 3 Unclassifiable as to its carcinogenicity in humans 503 Don t know inadequate 0 Group 4 Probably not carcinogenic to humans 1 No lack Can we reduce riskincidence YES Legislation Public pollution prevention strategies gov t ban of burden of compounds chemicals etc Individual 0 Reduce exposure to known or suspected carcinogens 0 Removereduce interacting compounds tobacco use as a mine worker 0 Increase exposure to anticarcinogens
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