Env-107 - Lecture noteProf. Dr. Md. Anisur Rahman Khan (ARK)

ENVIRONMENTAL HEALTH

Health : The World Health Organization (WHO) defines health as a state of complete physical, mental, and social wellbeing, not merely the absence of disease or infirmity. By that definition, we all are ill to some extent. Likewise, we all can improve our health to live happier, longer, more productive, and more satisfying lives if we think about what we do.

Disease : A disease is an abnormal change in the body's condition that impairs important physical or psychological functions. Diet and nutrition, infectious agents, toxic substances, genetics, trauma, and stress all play roles in morbidity (illness) and mortality (death). Environmental health focuses on external factors that cause disease, including elements of the natural, social, cultural, and technological worlds in which we live.

In the past, health organizations have focused on the leading causes of death as the best summary of world health. Mortality data, however, fail to capture the impacts of nonfatal outcomes of disease and injury, such as dementia or blindness, on human well-being.

When people are ill, work isn't done, crops aren't planted or har vested, meals aren't cooked, and children can't study and learn. Health agencies now calculate disability-adjusted life years (DALYs) as a measure of disease burden. DALYs combine premature deaths and loss of a healthy life resulting from illness or disability. This is an attempt to evaluate the total cost of disease, not simply how many people die.

A full understanding of health requires that humanity be seen as part of an ecosystem. The human ecosystem includes in addition to the - natural environment, all the dimensions of the man-made environment - physical, chemical, biological, psychological: in short, our culture and all its products. Disease is embedded in the ecosystem of man. Health, according to ecological concepts, is visualized as a state of dynamic equilibrium between man and his environment.

By constantly altering his environment or ecosystem by such activities as urbanization, industrialization, deforestation, land degradation, construction of irrigation canals and dams, man has created for himself new health problems. For example, the greatest threat to human health in India today is the ever-increasing, unplanned urbanization, growth of slums and deterioration of environment. As a result, diseases at one time thought to be primarily "rural" (e.g., filariasis, leprosy) have acquired serious urban dimensions. The agents of a number of diseases, for example, malaria and kala-azar, which were effectively controlled have shown a recurrence. The reasons for this must be sought in changes in the human ecology. Man's intrusion into ecological cycles of disease has resulted in zoonotic diseases such as rabies, yellow fever, monkeypox, lassa fever, etc.

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The Bhopal gas tragedy in 1984 highlights the danger of locating industries in urban area. The nuclear disaster in Soviet Russia in April 1986 is another grim reminder of environmental pollution. The construction of dams, irrigation systems and artificial lakes has created ecological niches favouring the breeding of mosquitos, snails and spread of filariasis, schistosomiasis and Japanese encephalitis. In fact, ecological factors are at the root of the geographic distribution of disease. Therefore it. has been said that good public health is basically good ecology.

Some have equated ecology with epidemiology. The main distinction between epidemiology and ecology is that while epidemiology is the study of the relationship between variations in man's environment and his state of health (or disease), ecology embraces the interrelationship of all living things. In this regard, epidemiology constitutes a special application of human ecology or that part of ecology relating to the state of human health.

It is now being increasingly recognized that environmental factors and ecological considerations must be built into the total planning process to prevent degradat!on of ecosystems. Prevention of disease through ecological or environmental manipulations or interventions is much safer, cheaper and a more effective rational approach than all the other means of control. It is through environmental manipulations that diseases such as cholera, typhoid, malaria and hookworm disease could be brought under control or eliminated. The greatest improvement in human health thus may be expected from an understanding and modification of the factors that favour disease occurrence in the human ecosystem.

It was Hippocrates who first related disease to environment e.g., air, water, climate etc. Centuries later, Pettenkofer in Germany revived the concept of disease environment association.

Environment is classified as "internal" and "external". The internal environment of man pertains to each and every component, part, every tissue, organ and organ system and their harmonius functioning within the system. The external or macroenvironment consists of all those components to which man is exposed after conception. It is defined as "all that which is external to the individual human host", living or nonliving, and with which he is in constant interaction. For descriptive purposes, the environment of man has been divided into three components

(1) Physical environment,(2) Biological environment, and(3) Psycho-social environment

All of these can affect the health of man and his susceptibility to a disease.

Biological environment includes all living things viz: viruses and other microbialagents, insects, rodents, animals and plants. These are constantly struggling for theirsurvival, and in this process some of them act as disease producing agents, reservoirs of infection, intermediate hosts and vectors of disease. For the most part, the partners manage to affect a harmonius inter-relationship, to achieve a peaceful co-existence. However, if for any reason this harmonius relationship is disturbed, ill health results. Biological agents of disease include viruses, rickettsiae, fungi, bacteria, protozoa and metazoa. A wide

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variety of pathogens (disease-causing organisms) afflict humans, including viruses, bacteria, protozoans (singlecelled animals), parasitic worms, and flukes. Probably the greatest loss of life from an individual disease in a single year was the great influenza epidemic of 1918.

These agents exhibit following biological properties.

i. Infectivity: This is the ability of an infectious agent to produce an infection in the host.

ii. Pathogenicity: This is the ability to induce clinically apparent illness.

iii. Virulence: This is defined as the proportion of clinical cases resulting in severe clinical manifestations.

Infectious Diseases, Environment and EcologyAn everchanging scenario of infectious disease persists in rich and poor countries, particularly the latter. Emerging and re-emerging diseases are an index of large scale environmental change. The rise of HIV/AIDS throughout the world, especially in third world, cholera in Peru and Equador related to blue-green algal blooms, the emergence of V-cholerae 0139 in South Asia, the re-emergence of malaria, kala-azar and plague in India, the accentuation of tuberculosis in many developing countries and the recent spread of viral hemorrhagic fevers in the wake of deforestation and extension of agricultural irrigation, the recent increase in antibiotic resistance of a variety of microbial pathogens, are the indicators of environmental borne diseases.

Infection: The entry and development or multiplication of an infectious agent in the body of man or animals is known as infection. A clinically manifested disease of man or animals resulting from an infection is known as infectious disease. However, an illness due to a specific infectious agent or its toxic products capable of being directly or indirectly transmitted from man to man, animal to animal or from environment to man or animal is called as communicable disease. A communicable disease is transmitted from the source of infection to the host. Basically there are three links in the chain of transmission viz. the reservoir, modes of transmission and the susceptible host. A reservoir is defined as any person, animal, arthropod, plant, soil or substance (or a combination of these) in which an infectious agent lives, multiplies and on which it depends for survival and where it reproduces itself in such a manner that it can be transmitted to a suitable host In short, reservoir is the natural habitat of the organisms.

The reservoir may be of three types—i. Human reservoirii. Animal reservoir andiii. Reservoir in non-living things

Infectious diseases, spread from the interactions between individuals and food, water, air, or soil, constitute some of the oldest health problems that humans face. Today, infectious diseases have the potential to pose rapid local to global threats by spreading in hours through airplane travelers. Terrorist activity may also spread diseases Inhalation anthrax,

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caused by a bacterium. Diseases that can be controlled by manipulating the environment, such as by improving sanitation or treating water, are classified as environmental health concerns. Although there is great concern about the toxins and carcinogens produced in industrial society today, the greatest mortality in developing countries is caused by environmentally transmitted infectious disease.

In the world millions of cases of water-borne illness and food poisoning occur each year. These diseases can be spread by people; mosquitoes or fleas; or contact with contaminated food, water, or soil. They can also be transmitted through ventilation systems in buildings.

Mode of Transmission

Communicable diseases may be transmitted from the reservoir or source of infection to a susceptible individual in many different ways depending upon the infectious agent, port of entry and the local ecological conditions. As a rule infectious disease is transmitted by only one route. The mode of transmission of infectious diseases may be classified as follows.

(1) Direct transmission(a) Direct contact(b) Droplet infection(c) Contact with soil(d) Inoculation into skin or mucosa(e) Transplacental

(2) Indirect transmission(a) Vehicle born (b) Vector borne

(i) Mechanical (ii) Biological

(c) Air borne (d) Fomite borne(e) Unclean hands and fingers

Emergent and Infectious Diseases: Although the ills of modern life have become the leading killers almost everywhere in the world, communicable diseases still are responsible for about one-third of all disease-related mortality. Diarrhea, acute respiratory illnesses, malaria, measles, tetanus, and a few other infectious diseases kill about 11 million children under age five every year in the developing world. Better nutrition, clean water, improved sanitation, and inexpensive inoculations could eliminate most of those deaths

Emergent diseases are those not previously known or that have been absent for at least 20 years. The story of SARS is a good example of an emergent disease. Although coronaviruses have long been known to cause a variety of diseases some lethal-in animals, and two members of this virus family cause about 30 percent of all human colds, the particularly virulent form that appears to have jumped from wild animals to humans in

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southern China had been previously unknown to science. Similarly, in 2004 an avian flu spread from domestic poultry to humans and then spread rapidly through Southeast Asia. Although only about 24 people died, millions of ducks and chickens were slaughtered to stop the spread of the disease. Altogether, one-third of all global meat exports were banned in 2004 due to bird flu and other emergent diseases.

The largest recent human death toll from an emergent disease is due to HIV/AIDS. Although it was first recognized in the early 1980s, acquired immune deficiency syndrome has now become the fifth greatest cause of contagious deaths. The WHO estimates that more than 60 million people are now infected with the human immune-deficiency virus and that 3 million die every year from AIDS complications.

Although two-thirds of all current HIV infections are now in sub-Saharan Africa, the disease is spreading rapidly in South and East Asia. Over the next 20 years, there could be an additional 65 million AIDS deaths.

Major Types of Hazards

The various kinds of hazards we face can be categorized as follows:

• Cultural hazards such as unsafe working conditions, smoking, poor diet, drugs, drinking, driving, criminal assault, unsafe sex, and poverty.

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• Chemical hazards from harmful chemicals in the air, water, soil, and food. The bodies of most human beings contain small amounts of about 500 synthetic organic chemicals-whose health effects are mostly unknown-that did not exist in 1920.

• Physical hazards such as ionizing radiation, fire, earthquake, volcanic eruption, flood, tornadoes, and hurricanes.

• Biological hazards from pathogens (bacteria, viruses, and parasites), pollen and other allergens, and animals such as bees and poisonous snakes.

According to a 1998 study by Cornell University scientist David Pimentel, environmental factors such as malnutrition, smoking, cooking fires, skin cancer, exposures to pesticides and other hazardous chemicals, and air and water pollution contribute to about 40% of the world's annual deaths.

CHEMICAL HAZARDS

Toxic and Hazardous Chemicals: Toxic chemicals generally are defined as substances that are fatal to more than 50% of test animals (LD50) at given concentrations. Hazardous chemicals cause harm by (1) being flammable or explosive, (2) irritating or damaging the skin or lungs (strong acidic or alkaline substances such as oven cleaners), (3) interfering with or preventing oxygen uptake and distribution (asphyxiants such as carbon monoxide and hydrogen sulfide), or (4) inducing allergic reactions of the immune system (allergens).

Mutagen: Mutagens are agents, such as chemicals and ionizing radiation, that cause random mutations, or changes, in the DNA molecules found in cells. Mutations in a sperm or egg cell can be passed on to future generations and cause diseases such as (1) bipolar disorder, (2) cystic fibrosis, (3) hemophilia, (4) sickle-cell anemia, (5) Down syndrome, and (6) some types of cancer. Mutations in other cells are not inherited but may cause harmful effects.

Most mutations are harmless, probably because all organisms have biochemical repair mechanisms that can correct mistakes or changes in the DIVA code. fnaddition, some mutations play a vital role in microevolution.

Teratogens: Teratogens are chemicals, radiation, or viruses that cause birth defects while the human embryo is growing and developing during pregnancy, especially during the first 3 months. Chemicals known to cause birth defects in laboratory animals include (1) PCBs, (2) thalidomide, (3) steroid hormones, and (4) heavy metals such as arsenic, cadmium, lead, and mercury.

Carcinogens: Carcinogens are chemicals, radiation, or viruses that cause or promote the growth of a malignant (cancerous) tumor, in which certain cells multiply uncontrollably. Many cancerous tumors spread by metastasis when malignant cells break off from tumors and travel in body fluids to other parts of the body. There, they start new tumors, making

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treatment much more difficult. According to the WHO, environmental and lifestyle factors play a key role in causing or promoting up to 80% of all cancers. Major sources of carcinogens are (1) cigarette smoke (30-40% of cancers), (2) diet (20-30%), (3) occupational exposure (5-15%), and (4) environmental pollutants (1-10%). Inherited genetic factors and certain viruses cause about 10-20% of all cancers.

Typically, 10-40 years may elapse between the initial exposure to a carcinogen and the appearance of detectable symptoms. Partly because of this time lag, many healthy teenagers and young adults have trouble believing that their smoking, drinking, eating, and other lifestyle habits today could lead to some form of cancer before they reach age 50.

BIOLOGICAL HAZARDS: DISEASE IN DEVELOPED AND DEVELOPING COUNTRIES

Nontransmissible Diseases: A nontransmissible disease is not caused by living organ-isms and does not spread from one person to another. Examples are (1) cardiovascular (heart and blood vessel) disorders, (2) most cancers, (3) diabetes, (4) asthma, (5) emphysema, and (6) malnutrition. Such diseases typically have multiple (and often unknown) causes and tend to develop slowly and progressively. The world's population is growing and getting older. Thus, the incidence of and deaths from many nontransmissible diseases (especially cardiovascular disorders and cancers) are expected to increase.

Transmissible Diseases: A transmissible disease is caused by a living organism (such as a bacterium, virus, protozoa, or parasite) and can be spread from one person to another. These infectious agents, called pathogens, are spread by air, water, food, body fluids, some insects, and other nonhuman carriers called vectors.

Factors that Affect the Spread of Transmissible Diseases: Outbreaks of infectious diseases often occur because of a change in the physical, social, or biological environment of disease reservoirs, carrier vectors, or exposure to new host populations. Important factors include the following:

Increased international air travel.• Migration to urban areas, which increases the probability of infection from diseases such as TB (Case Study, above), cholera, and STDs.

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• Migration to uninhabited rural areas and deforestation in tropical developing countries, which can expose people to new diseases and disease vectors such as malaria, sleeping sickness, and yellow fever.• Migration to suburbs in developed countries. For example, as more people have moved to wooded suburbs in the eastern United States, they have come into greater contact with ticks infested with bacteria that cause Lyme disease, which causes fever, lethargy, and (sometimes) long-lasting arthritis.• Hunger and malnutrition, which increase the number of children killed by infectious diseases such as measles and diarrhea.• Increased rice cultivation in flooded fields and paddies, which creates ideal breeding grounds for mosquitoes and other insects that transmit diseases to humans.• Global warming, which is leading to the spread of tropical infectious diseases such as malaria, yellow fever, and dengue fever (called "breakbone fever" by those who experience the excruciating pain it causes in joints) to temperate areas.• High winds or hurricanes, which can transfer infectious organisms and carriers of disease (such as insects) from tropical to temperate areas.• Accidental introduction of insect vectors. The Asian tiger mosquito is a vector for dengue fever, yellow fever, and other viruses. In 1985, it was brought accidentally to the United States inside used tires shipped from Asia. Since then, this mosquito species has spread from Texas to at least 21 other states.• Deliberate introduction of pathogens as an act of bioterrorism. This occurred in 2001 when strains of potentially fatal anthrax bacteria were introduced into the United States, mostly through deliberately contaminated letters and packages.• Flooding, which (1) often contaminates water supplies with raw sewage and (2) creates areas of standing water and moist soil that are ideal breeding grounds for mosquitoes and other insects that spread infectious diseases.

Toxicology

Toxicology is the study of toxins (poisons) and their effects, particularly on living systems. Because many substances are known to be poisonous to life (whether plant, animal, or microbial), toxicology is a broad field, drawing from biochemistry, histology, pharmacology, pathology, and many other disciplines. Toxins damage or kill living organisms because they react with cellular components to disrupt metabolic functions. Because of this reactivity, toxins often are harmful even in extremely dilute concentrations. In some cases, billionths, or even trillionths, of a gram can cause irreversible damage.

All toxins are hazardous, but not all hazardous materials are toxic. Some substances, for example, are dangerous because they’re flammable, explosive, acidic, caustic, irritants, or sensitizers. Many of these materials must be handled carefully in large doses or high concentrations, but they can be rendered relatively doses or high concentrations, but they can be rendered relatively innocuous by dilution, neutralization, or other physical treatment. They don’t react with cellular components in ways that make them poisonous at low concentrations.

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Environmental toxicology, or ecotoxicology, specifically deals with the interactions, transformation, fate, and effects of natural and synthetic chemicals in the biosphere, including individual organisms, populations, and whole ecosystems. In aquatic systems the fate of the pollutants in primarily studied in relation to mechanisms and processes at interfaces of the ecosystem components. Special attention is devoted to the sediment/water, water/organisms, and water/air interfaces. In terrestrial environments, the emphasis tends to be on effects of metals on soil fauna community and population characteristics.

Table 8.3 is a list of the top 20 toxins compiled by the U.S. Enviromental Protection Agency from the 275 substances regulated by the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), commonly known as the Superfund Act. These materials are listed in order of assessed importance in terms of human and environmental health.

Allergens are substances that activate the immune system. Some allergens act directly as antigens; that is, they are recognized as foreign by white blood cells and stimulate the production of specific antibodies (proteins that recognize and bind to foreign cells or chemicals). Other allergens act indirectly by binding to and changing the chemistry of foreign materials so they become antiseepic and cause an immune response.

Formaldehyde is a good example of a widely used chemical that is a powerful sensitizer of the immune system. It is directly allergenic and can trigger reactions to other substances. Widely used in plastics_ wood products, insulation, glue, and fabrics, formaldehyde concentrations in indoor air can be thousands of times higher than in nornrtl outdoor air. Some people suffer from what is called sick building syndrome: headaches allergies, and chronic fatigue caused by poorly vented indoor air contaminated by molds, carbon monoxide. nitrogen oxides, formaldehyde, and other toxic chemi -cals released by carpets, insulation, plastics, building materials, and other sources.

TABLE 8.3 : Top 20 Toxic and Hazardous Substances

1. Arsenic2. Lead3. Mercury4. Vinyl chloride5. Polychlorinated biphenyls (PCBs)6. Benzene7. Cadmium8. Benzo(a)pyrene9. Polycyclic aromatic hydrocarbons 10. Benzo(b)fluoranthene 11. Chloroform12. DDT13. Aroclor 1254 14. Aroclor 1260

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15. Trichloroethylene16. Dibenz(a,h)anthracene 17. Dicldrin18. Chromium, hcxavalcnt 19. Chlordane 20. Hexachlorobutadiene

Neurotoxins are a special class of metabolic poisons that specifically attack nerve cells (neurons). The nervous system is so important in regulating body activities that disruption of its activities is especially fast-acting and devastating. Different types of neurotoxins act in different ways. Heavy metals, such as lead and mercury, kill nerve cells and cause permanent neurological damage. Anesthetics (ether, chloroform, halothane, etc.) and chlorinated hydrocarbons (DDT, Dieldrin, Aldrin) disrupt nerve cell membranes necessary for nerve action. Organophosphates (Malathion, Parathion) and carbamates (carbaryl, zeneb, maneb) inhibit acetylcholinesterase, an enzyme that regulates signal transmission between nerve cells and the tissues or organs they innerc7 (for example, muscle). Most neurotoxins are both acute and extremely toxic. More than 850 compounds are now recognized as neurotoxins.

Mutagens are agents, such as chemicals and radiation, that damage or alter genetic material (DNA) in cells. This can lead to birth defects if the damage occurs during embryonic or fetal growth. Later in life, -enetic damage may trigger neoplastic (tumor) growth. When damage occurs in reproductive cells, the results can be passed on to future generations. Cells have repair mechanisms to detect and restore damaged genetic material, but some changes may be hidden, and the repair process itself can be flawed. It is generally accepted that there is no "safe" threshold for exposure to mutagens. Any exposure has some possibility of causing damage.

Teratogens are chemicals or other factors that specifically cause abnormalities during embryonic growth and development. Some compounds that are not otherwise harmful can cause tragic problems in these sensitive stages of life. Perhaps the most prevalent teratogen in the world is alcohol. Drinking during pregnancy can lead to fetal alcohol syndrome a cluster of symptoms including craniofacial abnormalities, developmental delays, behavioral problems, and mental defects, that last throughout a child's life. Even one alcoholic drink a day during pregnancy has been associated with decreased birth weight.

Carcinogens are substances that cause cancer-invasive, out-of-control cell growth that results in malignant tumors. Cancer rates rose in most industrialized countries during the twentieth century, and cancer is now the second leading cause of death in the United States, killing more than half a million people in 2000. Twenty-three of the 28 compounds listed by the U.S. EPA as greatest risk to human health are probable or possible human carcinogens. More than 200 million people live in areas where the combined upper limit lifetime cancer risk from these carcinogens exceeds 10 in I million, or 10 times the risk normally considered acceptable.

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Concept of Dose and Response

Five Centuries ago, the physician and alchemist Paracelsus wrote that everything is poisonous, yet nothing is poisonous." By this, he meant essentially that a substance in too great an amount can be dangerous yet in all extremely small amount can be relatively harmless. Every chemical element has a spectrum of possible effects on a particular organism. For example, Selenium is required in small amounts by living things but may be toxic or increase the probability of cancer in cattle and wildlife when it is pres ent in high concentrations in the soil. Copper, chromium, and manganese are other chemical elements required 'in small amounts by animals but toxic in higher amounts.

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It was recognized many years ago that the effect of a certain chemical on an individual depends on the dose. This concept is termed dose response. Dose dependency can be represented by a generalized dose-response Curve such as that shown in Figure 15.11.

When various concentrations of a chemical present in i biological system are plotted against the effects on the organism, two things arc apparent. First, relatively large concentrations are toxic and even lethal (points D, E, and Fin Figure 15.12). Second, trace concentrations may be beneficial for life (between points A and D); and the dose-response curve forms a plateau of optimal concen-tration and maximum benefit between two points (B and ("). Points A, B, C, D, E, and F in Figure 15.11 areimportant thresholds in the dose-response curve. Unfortunately,, the amounts at which points E- and F occur are known only for a few substances, for a few organisms, including people; and the very important point D is all but unknown. Doses that arc beneficial, harmful, or lethal may differ widely for different organisms and are difficult to characterize.

Fluorine provides a good example of the general dose-response concept. Fluorine forms fluoride compounds that prevent tooth decay and promote the development of a healthy, bone structure.

Relationships between the concentration of fluoride (in a compound of fluorine, such as sodium fluoride, NaF) and health show a specific dose-response curve (Figure 15.12). The plateau for an optimal concentration of fluoride (point B to point C) to reduce dental caries (cavities) is from about 1 ppm to just less than 5 ppm. Levels greater than 1.5 ppin do not

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significantly decrease tooth decay but do increase the occurrence of discoloration of teeth. Concentrations of 4 to 6 ppm reduce the prevalence of osteoporosis, a disease characterized bv loss of bone mass; and toxic effects are noticed between 6 and 7 ppm (point D in Figure 15.12).

Dose-Response Curve (LD-50, ED-50, and TD-50)

Individuals differ in their response to chemicals, and it is difficult to predict the dose that will cause a response in a particular individual. For this reason, it is practical to predict what percentage of a population will respond to a specific dose of a chemical.

For example, the dose at which 50% of the population die is called the lethal dose 50, or LD-50. The LD-50 is a crude approximation of a chemical's toxicity. It is a gruesome index that does not adequately convey the sophistication of modern toxicology and is of little use in setting a standard for toxicity. However, the LD-50 determination is required for new synthetic chemicals as a way of estimating their toxic potential. Table 15.4 lists, as examples, LD-50 values in rodents for selected chemicals.

The ED-50 (effective dose 50%) is the dose that causes an effect in 50% of the population of observed subjects. For example, the ED-50 of aspirin would be the dose that relieves headaches in 50% of the people.3ll

The TD-50 (toxic dose 50%) is defined as the dose that is toxic to 50% of the population. TD-50 is often used to indicate responses such as reduced enzyme activ ity, decreased reproductive success, or onset of specific symptoms, such as loss of hearing,

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nausea, or slurred speech.

For a particular chemical, there may be a whole family of dose-response Curves, as illustrated in Figure 15.13. Which dose is of interest depends on what is being evaluated. For example, for insecticides we may, wish to know the dose that will kill 100% of the insects exposed; therefore the LD-95 (the dose that kills 95% of the insects) may be the minimum acceptable level. However, when considering human health and the exposure to a particular toxin, we often want to know the Lll-0-thc maximum dose that does not cause any deaths.3° For potentially toxic compounds such as insecticides, which may form a residue on food or food additives, wc want to ensure that the expected levels of human exposure will have no known toxic effects. From an environmental perspective, this is important because of concerns about increased risk of can cer associated with exposure to toxic agents.30

Table 15.4 Approximate LD-50 Values (for rodents) for Selected AgentsAgent LD50(mg/kg)nSodium chloride (table salt) 4,000Ferrous sulfate (to treat anemia) 1,5202,4-D (a weed killer) 368DDT (an insecticide) 135Caffeine (in coffee) 127Nicotine (in tobacco 24Strychnine sulfate (used to kill certain pests)

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Bonilinum toxin (in spoiled food) 0.00001

Milligrams per kilogram of body mass (termed mass weight, although it really isn't a weight) administered by mouth to rodents. Rodents are commonly used in such evaluations, in part because they are mammals (as we arc), are small, have a short life expectancy, and their biology is well known

Source: H. B. Schiefer, D. C. Irvine, and S. C. Buzik,Uszderstrysadinq Trixicola_qy (Ncw York: CRC Press, 1997).

For drugs used to treat a particular disease, the effi ciency of the drug as a treatment is of paramount importance. In addition to knowing what the therapeutic value (ED-50) is, it is also important to know the relative safety of the drug. For example, there may be an overlap between the therapeutic dose (ED) and the toxic dose (TD) (see Figure 15.13). That is, the dose that causes a positive therapeutic response in some individuals might be toxic to others. A quantitative measure of the relative safety of a particular drug is the therapeutic index, defined as the ratio of the LD-50 to the ED-50. The greater the therapeutic index, the safer the drug is believed to be.- 3l In other words, a drug with a large difference bet-, ,,-ccii the lethal and therapeutic dose is safer than one with a smaller difference.

Threshold EffectsA threshold is a level below which no effect occurs and above which effects begin to

occur. If a threshold dose of a chemical exists, then a concentration of that chemical in

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the environment below the threshold is safe. If there is no threshold dose, then even the smallest amount of the chemical has some negative toxic effect (Figure 15.14).

Whether or not there is a threshold effect for environmental toxins is an important environmental issue. For example, the U.S. Federal Clean Water Act originally stared as a goal to reduce to zero the discharge of pollutants into water. The goal implies there is no such thing as a threshold effect, since no level of toxin is to be legally permitted. However, it is unrealistic to believe zero discharge of a water pollutant can be achieved or to believe that we can reduce to zero the concentration of chemicals shown to be carcinogenic.

A problem in evaluating thresholds for toxic pollutants is that it is difficult to account for synergistic effects. Little is known about if or how thresholds might change if an organism is exposed to more than one toxin at the same time or to a combination of toxins and other chemicals, some of which arc beneficial. Exposures of people to chemicals in the environment arc complex, and we are only beginning to understand and conduct research on the possible interactions and consequences of multiple exposures.

Ecological GradientsDose-responsc effects differ among species. For example, the kinds of vegetation that can live

nearest to a toxic source arc often small plants with relatively short lifetimes grasses, sedges, and weedy species usually regarded as pests) that arc adapted to harsh and highly variable envi-ronments. Farther from the toxic source, trees may be able to survive. Changes in vegetation with distance from a toxic Source define the ecological gradient.

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Ecological gradients may be found around smelters and other industrial plants that discharge pollutants into the atmosphere from smokestacks. For example, ccological gradient patterns can be observed in the area around the smelters of Sudbury, Ontario, discussed earlier in this chaptcr (A Closer I,ook 15.1). Near the smelters, an area that was once forest is now a patchwork of bare rock and soil Occupied by small plants.

ToleranceThe ability to resist or withstand stress resulting from exposure to a pollutant or harmful

condition is referred to as tolerance. Tolerance can develop for some pollutants in some populations, but not for all pollutants in all populations.

Tolerance may result from behavioral, physiological, or genetic adaptation. Behavioral tolerance results from changes in behavior. For example, mice learn to avoid traps.

Physiological tolerance results when the body of an individual adjusts to tolerate a higher level of pollutant. For example, in studies at the University of California Environmental Stress Laboratory, students were exposed to Ozone (O;), an air pollutant often present in large cities (Chapter 23). The students at first experienced svmptoms that included irritation of eyes and throat and Shortness of breath. However, after a few days, their bodics adapted to the ozone, and they reported that they believed they were no longer breathing ozonc-contaminated air, even though the concentration of 03 stayed the same. This phenomenon explains why some people who regularly breathe polluted air report that they do not notice the pollution. Of course, it does not mean that the ozone is doing no damage; it is, especially in people with existing respiratory problems. There arc many mechanisins for physiological tolerance, including deto:xifiecrtion, in which the toxic chemical is converted to a nontoxic form, and the internal transport of the toxin to a part of the body where it is not harmful, such as fat Cells.

Genetic tolerance, or adaptation, results when some individuals in a population are naturally more resistant to a toxin than others. They are less damaged by exposure and more successful in breeding. Resistant individuals pass on the resistance to future generations, who are also more successful at breeding. Adaptation has been observed among sonic insect Pests fOIIO\X'illg exposure to some chemical pesticides. For example, certain strains of malaria-causing mosquitoes are now resistant to DDT (see the discussion in Chapter 12); and some organisms that cause deadly infectious diseases have become resistant to common antibiotic drugs, Such as penicillin.

Acute and Chronic EffectsPollutants can have acute and chronic effects. An acute ef'f'ect is one that occurs soon after

exposure, usually to large amounts of a pollutant. A chronic effect takes place over a long period, often as a result of exposure to low levels of a pollutant. For example, a person exposed all at once to a high dose of radiation may be killed by radiation sickness soon after exposure (an acute effect). Howcver, that same total dose, received slowly in small amounts over an entire lifetime, may instead cause mutations and lead to disease or affect the person's DNA and offspring (a chronic effect).

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Risk AssessmentRisk assessment can be defined as the process of determining potential adverse environmental health effects to people exposed to pollutants and potentially toxic matcrials. Such an assessment generally includes four steps:

1. Identification of the hazard. Identification consists of testing materials to determine whether exposure is likeIN, to cause environmental health problems. One method used is to investigate populations of people who havc been previously exposed. For cxarrip1c, to understand the toxicity of radiation produced from radon gas, researchers Studied workers in uranium mines. Another method is to perform experiments to test effects on animals, Such as mice, rats, or monkeys. This method has drawn ina-casing criticism from groups of people who believe such experiments are unethical. Another approach is to trv to understand how a particular chemical works at the molcctilar level on cells. For example, research has been done to determine how dioxin interacts with living cells to produce an adverse response. After quantifying the response, scientists can develop mathematical models to predict or estimate dioxin's risk.l8 This relatively new approach might also be applicable to other potential toxins that work at the Cellular level.

2. Dose-responase assessment. The next step involves identifying relationships between the dose of a chemical (therapeutic drug, pollutant, or toxin) and the health effects to people. Some studies involve administering fairly high doses of a chemical to animals. The effects, such as illness or symptoms (rash, tumor development) are recorded for varying doses, and the results are used to predict the response in people. This is difficult, and the results arc controversial for several reasons:

This is difficult, and the results arc controversial for several reasons:

The dose that results in a particular response may be very small and subject to measurement errors.

There may be arguments over whether thresholds arc present or absent Experiments on animals such as rats, mice, or monkws ma\' not be directly applicable

to humans. The assessment may rely on probability and statistical analysis. Although statistically

significant results from experiments or observations are accepted as evidence to support an argument, statistics cannot establish that the substance tested caused the observed response.

3. Exposure assessment.. Exposure assessment evaluates the intensity, duration, and frequency of human exposure to a particular chemical pollutant or toxin. The hazard to society is directly proportional to the total population exposed. The hazard to an individual is generally greater closer to the source Of exposure. I,ilce dose-response assessment, exposure assessment is difficult, and the results are often controversial, in part because of difficulties in measuring the concentration of a toxin present in doses as small as parts per million, billion, or even trillion. Some questions that exposure assessment attempts to answer are:

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How many people were exposed to concentrations of a toxin thought to be dangerous How large an area was contaminated by the toxin,' What are the ecological gradients for exposure to the toxin? How long were people exposed to a particular toxin'

4. Risk characterization. During this final step, the goal is to delineate health risk in terms of the magnitude of the potential environmental health problem that might result from exposure to a particular pollutant or toxin. To do this, it is necessary to identify the hazard, complete the dose-response assessment, and evaluate the exposure assessment as outlined above. This step involves all the uncertainties of the prior steps, and results are again like ly to be controversial.

In summarv, risk assessment is difficult, costly, and controversial. Each chemical is different, and there is no one method of determining responses of humans for specific Ells or TDs. Toxicologists use the scientific method of hypothesis testing with experiments to generate predictions of how specific doses of a chemical may affect humans. Warning labels listing potential side effects of using a specific medication are required by, law, and these warnings result from tOXIC010p' Studies to determine a drug's safety.

Finally, risk assessment requires making scientific judgments and formulating actions to help minimize environmental health problems related to human exposure to pollutants and toxins. The process of risk managerment integrates the assessment of risk with technical, legal, political, social, and economic issues.1s Scientific arguments concerning the toxicity of a particular material are often open to debate. For example, there is debate concerning whether the risk from dioxin is linear. That is, do effects start at minimum levels of exposure to dioxin and gradually increase, or is there a threshold exposure beyond which environmental health problems occur?It is the task of people ill appropriate government agencies assigned to manage risk to make judgments and decisions based on the risk assessment and then to take appropriate actions to minimize the hazard resulting from exposure to toxins.

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