ntroduction to Toxicology (1)

A.

What is Toxicology? Toxicology is the study of how natural or man-made poisons cause undesirable effects in living organisms.
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What are harmful or adverse effects? Harmful or adverse effects are those that are damaging to either the survival or normal function of the individual. What is Toxicity? The word "toxicity" describes the degree to which a substance is poisonous or can cause injury. The toxicity depends on a variety of factors: dose, duration and route of exposure (see Module Two), shape and structure of the chemical itself, and individual human factors. Refer to Handout 1-1 General diagram of routes of exposure and Module Two Routes of Exposure [PDF - 1.3 MB]

1. B. What is Toxic? This term relates to poisonous or deadly effects on the body by inhalation (breathing), ingestion (eating), or absorption, or by direct contact with a chemical C. What is a Toxicant? A toxicant is any chemical that can injure or kill humans, animals, or plants; a poison. The term "toxicant" is used when talking about toxic substances that are produced by or are a by-product of human-made activities. For example, dioxin (2,37,8-tetrachlorodibenzo-p-dioxin {TCDD}), produced as a by-product of certain chlorinated chemicals, is a toxicant. On the other hand, arsenic, a toxic metal, may occur as a natural contaminant of groundwater or may contaminate groundwater as a byproduct of industrial activities. If the second case is true, such toxic substances are referred to as toxicants, rather than toxins. 1. What is a Toxin? The term "toxin" usually is used when talking about toxic substances produced naturally. A toxin is any poisonous substance of microbial (bacteria or other tiny plants or animals), vegetable, or synthetic chemical origin that reacts with specific cellular components to kill cells, alter growth or development, or kill the organism. 2. What is a Toxic Symptom? This term includes any feeling or sign indicating the presence of a poison in the system. 3. What are Toxic Effects? This term refers to the health effects that occur due to exposure to a toxic substance; also known as a poisonous effect on the body. 4. What is Selective Toxicity? "Selective toxicity" means that a chemical will produce injury to one kind of living matter without harming another form of life, even though the two may exist close together. 5. How Does Toxicity Develop? Before toxicity can develop, a substance must come into contact with a body surface such as skin, eye or mucosa of the digestive

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or respiratory tract. The dose of the chemical, or the amount one comes into contact with, is important when discussing how "toxic" an substance can be. 6. What is a dose? The dose is the actual amount of a chemical that enters the body. The dose received may be due to either acute (short) or chronic (long-term) exposure. An acute exposure occurs over a very short period of time, usually 24 hours. Chronic exposures occur over long periods of time such as weeks, months, or years. The amount of exposure and the type of toxin will determine the toxic effect. 7. What is dose-response? Dose-response is a relationship between exposure and health effect, that can be established by measuring the response relative to an increasing dose. This relationship is important in determining the toxicity of a particular substance (2). It relies on the concept that a dose, or a time of exposure (to a chemical, drug, or toxic substance), will cause an effect (response) on the exposed organism. Usually, the larger or more intense the dose, the greater the response, or the effect. This is the meaning behind the statement "the dose makes the poison." 8. What is the threshold dose? Given the idea of a dose-response, there should be a dose or exposure level below which the harmful or adverse effects of a substance are not seen in a population. That dose is referred to as the threshold dose'. This dose is also referred to as the no observed adverse effect level (NOAEL), or the no effect level (NEL). These terms are often used by toxicologists when discussing the relationship between exposure and dose. However, for substances causing cancer (carcinogens), no safe level of exposure exists, since any exposure could result in cancer. 9. What is meant by individual susceptibility?' This term describes the differences in types of responses to hazardous substances, between people. Each person is unique, and because of that, there may be great differences in the response to exposure. Exposure in one person may have no effect, while a second person may become seriously ill, and a third may develop cancer. 10. What is a "sensitive sub-population?" A sensitive sub-population describes those persons who are more at risk from illness due to exposure to hazardous substances than the average, healthy person. These persons usually include the very young, the chronically ill, and the very old. It may also include pregnant women and women of childbearing age. Depending on the type of contaminant, other factors (e.g., age, weight, lifestyle, sex) could be used to describe the population. The Field of Toxicology Toxicology addresses a variety of questions. For example, in agriculture, toxicology determines the possible health effects from exposure to pesticides or herbicides, or the effect of animal feed additives, such as growth factors, on people. Toxicology is also used in laboratory experiments on animals to establish dose-response relationships. Toxicology also deals with the way chemicals and waste products affect the health of an individual.

L.

Sub-disciplines of Toxicology

The field of toxicology can be further divided into the following subdisciplines or sub-specialities: Environmental Toxicology is concerned with the study of chemicals that contaminate food, water, soil, or the atmosphere. It also deals with toxic substances that enter bodies of waters such as lakes, streams, rivers, and oceans. This sub-discipline addresses the question of how various plants, animals, and humans are affected by exposure to toxic substances. Occupational (Industrial) Toxicology is concerned with health effects from exposure to chemicals in the workplace. This field grew out of a need to protect workers from toxic substances and to make their work environment safe. Occupational diseases caused by industrial chemicals account for an estimated 50,000 to 70,000 deaths, and 350,000 new cases of illness each year in the United States (1). Regulatory Toxicology gathers and evaluates existing toxicological information to establish concentration-based standards of "safe" exposure. The standard is the level of a chemical that a person can be exposed to without any harmful health effects. Food Toxicology is involved in delivering a safe and edible supply of food to the consumer. During processing, a number of substances may be added to food to make it look, taste, or smell better. Fats, oils, sugars, starches and other substances may be added to change the texture and taste of food. All of these additives are studied to determine if and at what amount, they may produce adverse effects. A second area of interest includes food allergies. Almost 30% of the American people have some food allergy. For example, many people have trouble digesting milk, and are lactose intolerant. In addition, toxic substances such as pesticides may be applied to a food crop in the field, while lead, arsenic, and cadmium are naturally present in soil and water, and may be absorbed by plants. Toxicologists must determine the acceptable daily intake level for those substances. Clinical Toxicology is concerned with diseases and illnesses associated with short term or long term exposure to toxic chemicals. Clinical toxicologists include emergency room physicians who must be familiar with the symptoms associated with exposure to a wide variety of toxic substances in order to administer the appropriate treatment. Descriptive Toxicology is concerned with gathering toxicological information from animal experimentation. These types of experiments are used to establish how much of a chemical would cause illness or death. The United States Environmental Protection Agency (EPA), the Occupational Safety and Health Administration (OSHA), and the Food and Drug Administration (FDA), use information from these studies to set regulatory exposure limits. Forensic Toxicology is used to help establish cause and effect relationships between exposure to a drug or chemical and the toxic or lethal effects that result from that exposure. Analytical toxicology identifies the toxicant through analysis of body fluids, stomach content, excrement, or skin.

Mechanistic Toxicology makes observations on how toxic substances cause their effects. The effects of exposure can depend on a number of factors, including the size of the molecule, the specific tissue type or cellular components affected, whether the substance is easily dissolved in water or fatty tissues, all of which are important when trying to determine the way a toxic substance causes harm, and whether effects seen in animals can be expected in humans.

1.

II.

Classification of Toxic Agents (2):

Toxic substances are classified into the following: A. Heavy Metals Metals differ from other toxic substances in that they are neither created nor destroyed by humans. Their use by humans plays an important role in determining their potential for health effects. Their effect on health could occur through at least two mechanisms: first, by increasing the presence of heavy metals in air, water, soil, and food, and second, by changing the structure of the chemical. For example, chromium III can be converted to or from chromium VI, the more toxic form of the metal. B. Solvents and Vapors Nearly everyone is exposed to solvents. Occupational exposures can range from the use of "white-out" by administrative personnel, to the use of chemicals by technicians in a nail salon. When a solvent evaporates, the vapors may also pose a threat to the exposed population. Have participants discuss possible solvents they use or may be exposed to during the course of a typical day. C. Radiation and Radioactive Materials Radiation is the release and propagation of energy in space or through a material medium in the form of waves, the transfer of heat or light by waves of energy, or the stream of particles from a nuclear reactor (3). An example for discussion purposes would be the dropping of the atomic bomb during World War II, or the Chernobyl Accident in Russia. These items can be provided by the presenter. D. Dioxin/Furans Dioxin, (or TCDD) was originally discovered as a contaminant in the herbicide Agent Orange. Dioxin is also a by-product of chlorine processing in paper producing industries.

E. Pesticides The EPA defines pesticide as any substance or mixture of substances intended to prevent, destroy, repel, or mitigate any pest. Pesticides may also be described as any physical, chemical, or biological agent that will kill an undesirable plant or animal pest (2). Have participants list pesticides they are familiar with either through personal use or in relation to hazardous chemicals in their community. F. Plant Toxins (2) Different portions of a plant may contain different concentrations of chemicals. Some chemicals made by plants can be lethal. For example, taxon, used in chemotherapy to kill cancer cells, is produced by a species of the yew plant. G. Animal Toxins (2) These toxins can result from venomous or poisonous animal releases. Venomous animals are usually defined as those that are capable of producing a poison in a highly developed gland or group of cells, and can deliver that toxin through biting or stinging. Poisonous animals are generally regarded as those whose tissues, either in part or in their whole, are toxic. Trainer may want to provide examples of venomous animals, such as snakes, spiders, etc., and poisonous animals, such as puffer fish, or oysters, which may be toxic to some individuals when contaminated with vibrio vulnificus. H. Subcategories of Toxic Substance Classifications All of these substances may also be further classified according to their: Effect on target organs (liver, kidney, hematopoietic system), Use (pesticide, solvent, food additive), Source of the agent (animal and plant toxins), Effects (cancer mutation, liver injury), Physical state (gas, dust, liquid), Labeling requirements (explosive, flammable, oxidizer), Chemistry (aromatic amine, halogenated hydrocarbon), or Poisoning potential (extremely toxic, very toxic, slightly toxic) I. General Classifications of Interest to Communities Air pollutants Occupation-related Acute and chronic poisons

All chemicals (or any chemical) may be poisonous at a given dose and through a particular route. For example, breathing too much pure oxygen, drinking excessive amounts of water, or eating too much salt can cause poisoning or death (1).

III.

Toxicological Information Sources (4)

A. The Agency for Toxic Substances and Disease Registry (ATSDR) ATSDR is part of the U.S. Department of Health and Human Services. It was created by Congress in 1980 to provide health-based information for use in the cleanup of chemical waste disposal sites mandated by the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). As the lead agency for implementing the health-related guidelines of CERCLA, ATSDR assesses the presence and nature of health hazards at specific Superfund Sites, to help prevent or reduce further exposure and the illnesses that result from such exposures, and to expand the knowledge-base about health effects from exposure to hazardous substances. ATSDR is mostly concerned with the health effects that may occur from exposure to toxic chemicals. ATSDR's Hazardous Substances and Health Effects Database (HazDat) discusses the issue. ATSDR also publishes Toxicological Profiles (which provide information on specific chemicals and possible health effects), Case Studies in Environmental Medicine (which are used to provide information to health care providers about the toxic effects of chemicals), and Public Health Statements (which contain information on toxic chemical exposures)(4). ATSDR's Division of Toxicology also produces ToxFAQs, a series of summaries about hazardous substances. Information for this series is excerpted from the ATSDR Toxicological Profiles and Public Health Statements. Each ToxFAQ summary is quick and easy to understand, and answers the most frequently asked questions (FAQs) about exposure to hazardous substances found around hazardous waste sites and the effects of exposure on human health. Medical Management Guidelines for Acute Chemical Exposures (Guidelines) were developed by ATSDR to aid emergency department physicians and other emergency healthcare professionals who manage acute exposures resulting from chemical incidents. The guidelines are intended to aid healthcare professionals involved in emergency response to effectively decontaminate patients, protect themselves and others from contamination, communicate with other involved personnel, efficiently transport patients to a medical facility, and provide competent medical evaluation and treatment to exposed persons. B. The United States Environmental Protection Agency (EPA) EPA is responsible for a number of activities, including enforcing federal laws designed to protect human health and the environment. There are ten regional EPA offices throughout the United States, with EPA headquarters located in Washington, D.C. Each regional office is responsible within selected states for implementing the agency's

programs, considering regional needs and implementing federal environmental laws. Following is a list of the regions and the states they cover. Refer to Figure 1.1 - Map of EPA Regional Offices
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[PDF - 2 MB]

Region 1: Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, Vermont Region 2: New Jersey, New York, Puerto Rico, and the U.S. Virgin Islands Region 3: Delaware, Maryland, Pennsylvania, Virginia, West Virginia, the District of Columbia Region 4: Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, Tennessee Region 5: Illinois, Indiana, Michigan, Minnesota, Ohio, Wisconsin Region 6: Arkansas, Louisiana, New Mexico, Oklahoma, Texas Region 7: Iowa, Kansas, Missouri, Nebraska Region 8: Colorado, Montana, North Dakota, South Dakota, Utah, Wyoming Region 9: Arizona, California, Hawaii, Nevada, the territories of Guam and American Samoa Region 10: Alaska, Idaho, Oregon, Washington

The specific chemicals regulated by EPA and the standards associated with them are found in the Code of Federal Regulations or CFR. The different sections of the CFR are called Titles, and the ones that apply to EPA are in Title 40 (1). EPA has developed rules and regulations that activate the requirements of several environmental laws provided below. Trainer Note: Refer to Table 1.1 which is a list of selected EPA laws that regulate chemicals in the environment. [PDF - 36 KB]
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In addition, the following EPA Laws regulate chemicals in the environment: The Clean Air Act implements regulations that control and abate air emissions from stationary and mobile sources. The Clean Water Act regulates discharge of pollutants to surface waters. The Safe Drinking Water Act establishes standards for contaminants in drinking water; regulates discharges to underground injection wells, sole source aquifers, and public drinking water systems. The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA or Superfund) deals with cleanup of hazardous waste sites and definition of requirements for response to hazardous waste spills. The Resource Conservation and Recovery Act (RCRA) deals with identification and regulation of hazardous waste treatment, storage, and disposal. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) requires registration and testing of pesticides, regulates their sale, distribution, and use. The Toxic Substances Control Act (TSCA) requires testing and reporting of chemicals prior to manufacturing, distribution, and use; and restricts the use of chemicals that pose a threat to human health and the environment.

The Emergency Planning and Community Right to Know Act (EPCRA) requires companies to report inventories of hazardous chemicals and toxic releases; and requires state and local governments to develop plans for responding to emergency releases.

In addition, EPA's Office of Research and Development (ORD) studies the effects of toxic exposure on people and the environment. C. The Centers for Disease Control and Prevention (CDC) CDC is an agency in the Department of Health and Human Services, its mission is to promote health and quality of life by preventing and controlling disease, injury, and disability. In the past, the CDC has focused on the study and prevention of infectious diseases such as malaria and smallpox. However, now its responsibilities have enlarged to include environmental and occupational hazards. Refer participants to Table 1.2 (Handout 1.3) - CDC Organizational Offices [PDF - 19KB] The CDC Centers that deal with environmental health are the National Center for Environmental Health (NCEH) and the National Institute for Occupational Safety and Health (NIOSH) (2). NCEH addresses hazards associated with chemical exposure inside and outside the workplace. NIOSH was established by the Occupational Safety and Health Act of 1970. NIOSH has several functions, including investigating potentially hazardous work conditions, and evaluating chemical hazards in the workplace. NIOSH is the only federal institute responsible for conducting research and making recommendations for the prevention of work-related illnesses and injuries. NIOSH's responsibilities include:
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Investigating potentially hazardous working conditions as requested by employers or employees, Evaluating hazards in the workplace, ranging from chemicals to machinery, Creating and disseminating methods for preventing disease, injury, and disability, Conducting research and providing scientifically valid recommendations for protecting workers; and Providing education and training to individuals preparing for or actively working in the field of occupational safety and health. Information gathered from these activities is used to help reduce disease, injury and disability in the workplace. The information is provided to OSHA, which uses it to establish standards to protect health in the workplace.

D. The Nuclear Regulatory Commission (NRC) (1) NRC, established in 1974, regulates the use of nuclear materials for commercial, industrial, academic, and medical purposes. This includes regulating nuclear power plants, nuclear materials used in the diagnosis and treatment of cancer, and nuclear

materials used in smoke detectors. NRC also regulates non-power research, test and training reactors; nuclear fuel cycle facilities (the production of nuclear fuel); and the transport, storage, and disposal of nuclear materials and waste. Like OSHA and EPA, NRC obtains and evaluates information about acceptable exposure levels for workers handling nuclear materials. E. The Food and Drug Administration (FDA) (5) FDA promotes and protects the public health by helping safe and effective products reach the market in a timely way, and monitoring products for continued safety after they are in use. F. The American Conference of Governmental Industrial Hygienists (ACGIH) ACGIH is a professional organization that produces a listing of Threshold Limit Values (TLV) and Biological Exposure Indices (BEI) for several hundred chemicals, updating them every year. BEIs are recommended maximum concentrations of various types of toxic substances, and are guidelines to evaluate the potential health hazards associated with exposure. The maximum concentration may be measured in blood, urine, or exhaled air. The TLVs are guidelines for occupational exposure to hazardous chemicals and are published in a booklet called Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents and Biological Exposure Indices (6). G. Electronic Databases Information on toxic chemicals is available at the following sites:
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Toxicology Data Network (TOXNET - www.toxnet.nlm.nih.gov ). Several databases, such as the Hazardous Substances Data Bank (HSDB) and the Registry of Toxic Effects of Chemical Substances (RTECS), can be found in the TOXNET database. The HSDB has toxicological information on more than 4,000 chemicals, as well as information on emergency handling procedures, environmental data, regulatory status, and human exposure. The RTECS is maintained by NIOSH and contains information on the health effects for more than 90,000 chemicals. CHEMTREC (Chemical Transportation Emergency Center - www.chemtrec.org ). CHEMTREC is provided by the American Chemistry Council (formerly known as the Chemical Manufacturer's Association) and provides information and assistance for emergency incidents involving chemicals and hazardous materials. CHEMTREC also supplies basic information about the production, shipping, and use of chemicals and provides information about medical treatment in response to chemical exposures. Material Safety Data Sheets (MSDS) are available on the Occupational Safety and Health Administration website: www.osha.gov . MSDSs provide information such as physical and chemical properties of a substance, first aid information, emergency response, and disposal information.

Hazardous Substances and Health Effects Database (HazDat), available on ATSDR's website at www.atsdr.cdc.gov. contains information on hazardous substances found at National Priorities List (NPL) and non-NPL waste sites and emergency events, and on the levels at which health effects from exposure to hazardous substances have been reported in humans and animals. HAZDAT contains environmental contamination and other data on more than 3,000 uncontrolled hazardous waste sites for which ATSDR has conducted public health assessments, prepared health consultations, or provided responses to emergencies involving releases of toxic substances into community environments. It contains toxicity information taken from the ATSDR's Toxicological Profiles for more than 200 substances most frequently found at sites (4).

I.

Types of Environments
Before one can understand the routes and pathways of exposure, it is important to have an understanding of the term "environment." Environment can be defined in a number of ways (7):
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Inner versus outer environment Personal versus ambient environment Gaseous, liquid, and solid environments Chemical, biological, physical, and socioeconomic environments

A. Inner Versus Outer Environment This refers to the human body and consists of the environment within the body and the environment outside of the body. The human body has three protective barriers against outside environmental contaminants. The skin, which protects the body from contaminants outside the body; The gastrointestinal (GI) tract, which protects the inner body from contaminants (toxins) that have been ingested, The membranes within the lungs, which protect the inner body from contaminants that have been inhaled. However, each of these barriers are liable to damage under certain conditions. Contaminants can penetrate to the inner body through the skin by dissolving the layer of wax that we have covering our oil (sebaceous) glands. The GI Tract is also very vulnerable to compounds that are soluble and can be easily absorbed and taken into the body cells. However, the body has ways of protecting the GI tract. For example, unwanted material can be vomited through the mouth, or rapidly excreted through the bowels (as in the case of diarrhea).

The lungs are the most important route for toxic substances, and they are also the most fragile. Airborne materials that are inhaled can be deposited in the lungs, and, if they are soluble, they can be absorbed. A number of mechanisms protect the lungs, such as, simple coughing, or cleansing by "macrophages" that engulf and promote the removal of anything foreign. Unless a toxicological agent or environmental contaminant penetrates one of the three barriers that protect the body, it will not get into the inner environment, and even if it does get in, there are other ways to remove it. For example, materials entering the circulatory system (arteries, veins, etc.) can be detoxified in the liver or excreted through the kidneys. B. Personal Versus Ambient Environment Your personal environment represents the environment that you can control. The ambient (working) environment represents the environment over which you have no control. It is thought that the working environment poses the greatest threat to health, but some health experts believe that the personal environment, influenced by a number of factors, is the most important for our well being. Factors which are important for the personal environment include hygiene, diet, sexual practices, exercise, use of tobacco, drug and alcohol use, and frequency of medical checkups. C. Gaseous, Liquid, and Solid Environments Our environment exists in one of three forms: gas, liquid, or solid, each of which can be polluted. Particulate (large particles) and gases are released into the air (gaseous), sewage and liquid wastes are discharged into water (liquid); and solid wastes, such as plastics and toxic chemicals are disposed of on land (solid). People interact with all of these environments. D. Chemical, Biological, Physical, and Socioeconomic Environments These types of environments could affect people's health. Chemical factors and contaminants include toxic wastes and pesticides in the environment; chemicals used at home (cleaning products) and by industry; and preservatives for food. Biological factors include different forms of disease organisms in food and water, and those that can be transmitted by insects and animals, and person-to-person contact. Physical factors include elements that may influence health and wellbeing, such as injuries and deaths from accidents, loud and excessive noise, extreme temperatures (heat and cold), and the effects of radiation. Socioeconomic factors - are hard to measure, but significantly affect the lives and the health of people. Low socioeconomic status increases death and illness rates. 2.

III.

Routes of Exposure
It has been estimated that about 70,000 chemicals are used worldwide, and the chemical industry introduces about 200 to 1,000 new chemicals each year (8). Because of this, we

are exposed to a number of chemicals in our home, at work, and in the general environment. Trace amounts of toxic chemicals are present in the food, the air, and the drinking water. Exposure to toxic substances occurs through the three major routes listed below. Refer to Handout 2.1. Routes of Exposure
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The skin (dermal absorption) The respiratory tract (inhalation) The digestive tract (ingestion) D. Dermal Absorption Contact with the skin is the most common path of toxic substance exposure (1). The skin is composed of three layers: Epidermis (outer layer). The outermost layer is the stratum corneum (carnified layer). This is the structure that determines the rate of absorption of substances through the epidermis. For example, a pesticide such as Malathion, which easily penetrates the stratum corneum, moves quickly through the other layers of the skin and is rapidly absorbed into the bloodstream. DDT, another type of pesticide, does not easily penetrate the stratum corneum, so the rate of absorption is much slower. Dermis (inner layer). The inner layer of the skin is sometimes referred to as the true skin. In animal hides, this is the layer that turns to leather when chemically processed. The dermis is the source of oxygen and of nutrients for the epidermis. The hair follicles, sweat glands, and sebaceous (oil) glands are found in this layer. These structures play a limited role in the absorption of substances across the skin. Subcutaneous fatty tissue. This layer provides a cushion for the underlying structures and allows the skin to move to some extent. Factors affecting dermal absorption of toxic substances include The condition of the skin. An intact stratum corneum (epidermis) is an effective barrier to absorption of some toxic chemicals. However, physical damage to the protective barrier, such as a cut or abrasion, allows toxic substances to penetrate the epidermis and enter the dermis where they more readily enter the bloodstream and are carried to other parts of the body. The chemical make up of the substance. Inorganic chemicals and substances are not easily absorbed through intact, healthy skin (such as cadmium, lead, mercury, and chromium. Organic chemicals dissolved in water do not easily penetrate the skin because the skin is impermeable to water. However, organic solvents, such as paint thinner or gasoline, are easily absorbed through the epidermis. Increasing the concentration of the toxic substance or the exposure time can increase the rate or amount of material absorbed. E. Inhalation

Inhalation is the easiest and fastest means of exposure to toxic substances because toxic substances are readily absorbed in the respiratory tract. The lining of the respiratory tract is NOT effective in preventing absorption of toxic substances into the body. The respiratory tract consists of the nasal passages, trachea (windpipe), larynx (voice box) and the lungs. The following factors affect inhalation of toxic substances: Concentration of toxic substance in the air, Solubility of substance in the blood and tissue, Respiration rate, Length of exposure, Condition of respiratory tract, and Size of toxic particle. F. Ingestion Ingestion of toxic substances usually occurs accidentally or unknowingly. The digestive tract consists of the mouth, the esophagus (food canal), stomach, and intestine (large and small). The major function of the digestive tract is to digest and absorb the foods we eat. Physical and chemical factors affect the absorption of toxic substances. Absorption is affected because of the structure of the body and the length of time food containing the substance remains in the body. Once a chemical is absorbed, its effects depend on its concentration in the target organs, its chemical and physical form, what happens to it after it is absorbed, and how long it remains in the tissue or organ of choice. After being taken up in the blood, a chemical is be quickly distributed throughout the body; it may be moved from one organ or tissue to another (translocation), or changed into a new compound (biotransformation). G. Other Routes of Exposure The eye is a common point of contact for toxic substances. The primary point of contact for toxic substances is the cornea. Acidic and basic compounds are the most common types of exposures that do damage. Depending on the amount of damage, the cornea may be able to repair itself. The outer layer of the eye is made up of connective tissue called the sclera. In the front of the eye, this forms into the cornea, which is transparent. The middle layer of the eye is called the choroid, which forms the iris, in the front of the eye. The innermost layer is the retina, which produces images. Two compartments within the eye contain a fluid-like substance called the aqueous humor, and a transparent jelly-like substance called the vitreous humor. All nutrients and oxygen must diffuse through the aqueous humor in the back to the cornea to repair the damaged tissue. Injections are another common route for exposure. Injections are mainly used in laboratory studies on experimental animals. Following are the different types of injections:

Intravenous injections (into a vein). Intramuscular injections (into the muscle). Intra peritoneal injections (into the abdominal cavity). Intradermal injections (into the skin). Subcutaneous injections (under the skin).

IV.

Elements for a Pathway of Exposure

ATSDR defines an exposure pathway as the process by which an individual is exposed to contaminants that originate from some source of contamination (9). For exposure to occur, a completed exposure pathway must exist. A completed exposure pathway exists when all of the following five elements are present:
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A source of contamination, for example a smoke stack on a factory; Media for the contaminant to travel, such as groundwater, surface soil, surface water, air, subsurface soil, sediment, and biota (animal and plant life); A point of exposure, or a place where people actually come into contact with the contaminated material; A route of exposure, or how contaminants enter or contact the body (i.e. ingestion, inhalation, dermal contact, and dermal absorption); and A receptor population, or those persons who are exposed or potentially exposed to the contaminants.

A potential exposure pathway exists when one or more of the elements is missing, but available information indicates that exposure is likely. An incomplete exposure pathway exists when one or more of the elements is missing and available information indicates that exposure is not expected to occur.

V.

Types of Exposure
Toxic chemicals generally produce the greatest effect and the most rapid response when inserted directly into the bloodstream (2). Occupational exposure generally occurs from breathing contaminated air (inhalation) and/or direct or extended contact of the skin with the substance (dermal exposure). In contrast, accidental and suicidal poisoning occurs most frequently by oral ingestion. The types of exposures are
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Acute, which is exposure to a chemical for 24 hours or less. Chronic, which is exposure to a chemical for more than 3 months. Sub-acute, which is exposure to a chemical for 1 month or less. Sub-chronic, which is exposure to a chemical between 1 to 3 months.

VI.

Effects After Exposure

Local effects are seen at or near the body part or parts where exposure occurred. For example, inhaling particles can result in irritation of the respiratory tract, resulting in effects ranging from sneezing to chest pains and difficulty in breathing. An ant bite leads to redness and swelling at the bite location.

Some substances are absorbed into the bloodstream and are then carried to other parts of the body, where they cause their effect. These types of substances usually cause their effect in one or two target body organs. Whether or not these effects occur depends on the concentration of the chemical in the target organ. The concentration in the organ is dependent on the absorption, distribution, biotransformation, and excretion of the substance. Biotransformation occurs when a substance is changed from one form to another, which may also change the toxic properties of the substance. It usually occurs in several steps, primarily in the liver, but it may also occur in other tissue like the kidneys, lungs, and digestive tract. Some substances are absorbed from the bloodstream and stored in tissues where they may not cause an adverse effect. For example, lead can be stored primarily in the long bones of the body, but when released, has a toxic effect on the nervous system.

VII.

Excretion of Toxins
The rate (speed) at which a toxic substance is removed from the body determines whether it will have a toxic effect. The longer a chemical is in the body, the greater the likelihood of damage. The main way a chemical is excreted from the human body is through the urine, but the kidneys, the lungs and the liver are also important in removing certain chemicals from the body. The kidney eliminates the greatest number of toxins than any other tissue/organ. The lungs eliminate substances that are in the gaseous phase, like carbon dioxide. The liver removes substances like lead or DDT (pesticide) by excreting them into bile, which is made by the liver and travels to the small intestine. From there the substance can be absorbed in the feces and then eliminated through excretion. Neither the sweat glands nor the GI tract are important routes for excreting of toxic substances (2). Skin, hair and breast milk are pathways, although minor, for excretion.

I.

What is Risk Assessment

First, risk is defined as the probability that an event will occur. It can also be defined as the probability that a health effect will occur after an individual has been exposed to a specified amount of a hazard. Risk assessment is the process of gathering all available information on the toxic effects of a chemical and evaluating it to determine the possible risks associated with exposure. The process of gathering and evaluating the information can be divided into the following:
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Hazard Identification Hazard Evaluation or Dose-Response Assessment Exposure Assessment Risk Characterization

A. Hazard Identification - this first step in risk assessment consists in collecting data from different sources to determine whether a substance is toxic. It involves gathering and examining data from toxicological and epidemiological studies.

Epidemiology' is the study of the causative factors that are associated with the occurrence and number of cases of disease and illness in a specific population. Information from these studies should answer these questions: Does exposure to the substance produce any adverse effects? If yes, what are the circumstances associated with the exposure? See Handout 3.1 - Types of information collected and considered when performing the risk assessment PDF [27 KB]. (Obtained from the U.S. Environmental Protection Agency, Risk Assessment Guidelines and Information Directory, Government Institute, Rockville, MD, 1988.)

Information collected and considered when performing a risk assessment are listed below.

Substance Identification (name) Physical/chemical properties of the toxic substance (Does it dissolve? Is it reactive [explosive, flammable, etc.], What is its size?) Source of the toxicity information

Epidemiological studies - The two major types of epidemiological studies are retrospective and prospective. Retrospective studies attempt to gather information from the past. Sometimes the information is incomplete because of the way the data was gathered. Because of that, it is sometimes difficult to determine if there is a relationship between the effect and a specific factor, such as exposure to a particular toxic substance. Prospective studies gather information from current, ongoing investigations. For that reason, the results are more complete and accurate than retrospective studies. Both methods are useful in identifying adverse health effects associated with a given toxic substance (1). Toxicological studies - Different types of studies fall under the category of toxicological studies, including acute toxicity studies, which look at short-term exposures, and chronic toxicity studies, which look at exposures over a long period of time.

Other factors to consider include the species of test animal (was the study done in rats, mice, man, etc.), and other variables affecting toxicity (including age, sex, and health of the study population). Exposure to Toxic Substances Exposure to toxic substances depends on the

Route of exposure (skin contact, inhalation, ingestion, injection),

Duration of exposure (acute or chronic), Frequency of exposure, and Exposure to other toxic substances. Other factors to consider when determining potential exposures to toxic substances include diet, lifestyle choices, and occupation.

B. Hazard Evaluation and Dose-Response Assessment If the hazard identification process produces evidence of a hazard, then a hazard evaluation is performed. The purpose of this step is to calculate, if possible, the dose at which a harmful effect will occur. Since an effect in animals may not be the same in humans, at the same dose, "safety factors" are used. Safety factors account for the differences in response of test animals and differences in toxicity. The dose-response assessment tells the toxicologist what dose causes a response, usually illness or death, in the test animal. C. Exposure Assessment An exposure assessment is performed to identify the affected population and, if possible, calculate the amount, frequency, length of time, and route of exposure. Exposure is "an event that occurs when there is contact at a boundary between a human and the environment at a specific (contaminant) for a specified period of time". Units to express exposure are "concentration times time"(1). Factors to consider when performing an exposure assessment include General information for each chemical - Identification of molecular formula and structure (how the chemical looks and is made) and other identifying characteristics - Chemical and physical properties Sources - Characterization of production and distribution - Uses - Disposal - Summary of environmental releases Exposure Pathways and Environmental Fate - Transport and transformation - Identification of principal pathways of exposure - Predicting environmental distribution Measured or Estimated Concentrations - Uses of measurements - Estimation of environmental concentrations Exposed Human Populations - Size and characteristics - Location - Habits

Integrated Exposure Analysis - Calculation of exposure includes identification of the exposed population and identification of pathways of exposure. D. Definition of Each Component in an Exposure Assessment General Information for Each Chemical - The physical/chemical properties of the toxic substance affects how it is transported, how it is accumulated in the environment and in tissues, and how it is transformed when it is released into the environment. Some examples of characteristics include: - vapor pressure (how easily can a chemical change from a solid or liquid to a gas?) - its ability to dissolve in water - its ability to stick to soil or sediments Knowing these facts will help determine the dose and route of exposure. Sources of Exposure - Exposure to chemicals can occur anywhere, including the home (cleaning products, paints, pesticides, etc.). Outside the home, exposure to chemical pollutants in the air occurs through inhalation. Exposure Pathways and Environmental Fate - Once the source has been identified, the route and nature of the exposure must be determined. For exposure could occur through drinking water (the route could be ingestion of contaminated water). Measured or Estimated Concentrations - If possible, it is best to obtain actual samples from the source of exposure to calculate the amount of toxic substance present. However, samples are not always available and estimations of exposure can be calculated using a mathematical model. These models attempt to estimate the concentration of a substance at the point of exposure. Modeling is mostly used when determining concentrations of substances in air, but can be used to determine the amount in lakes or other bodies of water. Exposed Population - It is important to identify and characterize the exposed population in terms of sex; age; number of small children, pregnant women, and chronically ill individuals. Other information such as eating, work, exercise, and play habits is also necessary. Some populations are more at risk for illness than others, such as young children and older adults. Measuring Exposures - The effects from exposure to simple and complex mixtures are very important, as well as the health impact of these substances on susceptible populations (e.g., children, elderly, people of color). Exposure can also vary greatly within geographic areas. Measurement of exposure is often determined through questionnaires or surveys, employment records, and evaluation of environmental contamination data for areas in which a study population lives (10). A problem seen in most communities is the absence of actual data, because no personal monitoring was conducted. This could lead to exposure calculations that could be too high or too low (10). How much exposure

occurred and how much of a dose a person received is significant in documenting exposure. Two major approaches for assessing total exposure include indirect methods and direct methods. Indirect methods include environmental monitoring; use of fate and transport (migration); computer models; (use of questionnaires, and/or surveys for residents). Direct methods, include the use of personal workplace monitoring equipment and biologic markers (2). The extent of exposure may depend on the size of the population, its proximity to the contamination source, a person's degree of personal contact with the site, and the extent of the release of hazardous substances. Children are one population particularly susceptible to the toxic effects of contaminants at hazardous waste sites. While playing outside, young children come into contact with environmental toxicants via dermal contact and subsequent hand-to-mouth activity. Therefore, children who play in areas where there is little to no vegetative cover, as in many urban areas, and pica children (those who ingest greater than an average amount of non-food items [dirt] per day) are particularly sensitive to contaminants in soil. Calculation of Exposure (1) - Once the information is available, exposure can be estimated. Exposure can occur through more than one route, and when that is the case, the total exposure may be measured by adding the contributions of all routes. When data is not available, certain guesses are made, using standard reference values. E. Risk Characterization The last and final step in the risk assessment process is putting all of the information gathered from the other steps together to determine the actual risk of exposure to a specific toxic substance. This step relies on the expertise of the assessor in analyzing the information. 2.

III.

Risk Management
Based on information obtained from the risk assessment, decisions are made about the best way to address environmental contamination and exposure. The risk manager also includes an evaluation of social, legal, economic, and policy issues to determine the best approach to address an exposure issue. ATSDR's public health assessment is an evaluation of environmental data, health outcome data, and community concerns associated with a site where hazardous substances have been released. The health assessment identifies populations living or working on or near hazardous waste sites for which more actions or studies are needed.

I.
A.

Introduction - Survey of Toxic Substances (1)

Outdoor Air Pollutants

While this module deals with specific substances, this section has the flexibility to include or substitute other chemicals, depending on the interest and concern of the particular community. For that reason, this section should be presented by an environmental health professional (toxicologist, an environmental health scientist, a health educator). In addition, one or two toxic substances may be the focus of the module. This particular module will require additional research by the trainer. EPA has focused its attention on the following outdoor pollutants, which may pose a health hazard from exposure (1): carbon monoxide, sulfur oxides, ozone, nitrogen oxides, and particulates. Other chemicals not listed, here, also have the potential to be toxic, however the focus is on the above listed chemicals because they are produced in the largest amount and/or have the greatest chance of producing a toxic effect. Levels of air pollutants are different at different times of the day, and are usually highest around midday, decreasing in the evening. An accidental release of a chemical could also increase levels.

Carbon Monoxide (CO) is a colorless, odorless, and tasteless gas produced by the burning of carbon or materials containing carbon. It is lighter than air and dissolves slightly in water. Some common sources of exposure to carbon monoxide include automobile exhaust and faulty or poorly ventilated charcoal, kerosene, or gas stoves. Foundries, coke ovens, and refineries are also sources, as are smoking tobacco products (2,11). Carbon monoxide decreases the amount of oxygen available to cells, resulting in problems with cell function. Short term (acute) exposure to CO at certain levels could cause a slight headache and shortness of breath. Exposure for longer periods (chronic) may cause headache, nausea, irritability, increased respiration, chest pain, impaired judgement, and fainting.

Sulfur oxides are a major source of air pollutants. They are produced from automobile exhaust, petroleum refineries, paper manufacturing, and chemical industries. The two types of sulfur oxides are sulfur dioxide (SO2) and sulfur trioxide (SO3). Sulfur dioxide is the main air pollutant of concern. It is an irritant colorless gas with a bitter taste, that dissolves in water to form sulfurous acid. It is a liquid under pressure and cannot catch fire. It

affects the eyes and the skin as well as the upper respiratory system, and is able to penetrate the lungs during mouth breathing as opposed to nose breathing. Sulfur dioxide in the air results mainly from activities associated with burning of coal or oil, such as power plants or copper smelting (12). The people most often affected by exposure are workers in plants where sulfur dioxide occurs as a by-product, such as in the copper smelting industry (12). Sulfur dioxide in the body is biotransformed (changed) into a breakdown product which can be measured in blood and urine. That way, exposure can possibly be determined (12). Ozone (O3) is a colorless gas and its odor can be detected at very low levels. It is formed as a result of the interaction between organic compounds, like ketones, aldehydes, and unsaturated hydrocarbons, and nitrogen oxides in the presence of sunlight. It is also formed by any other high-energy source, such as lightning, high voltage electrical equipment, and air- and water-purifying devices (1). Ozone is one of the major air pollutants in heavily industrialized areas and in cities with a large number of automobiles. More than half of the ingredients needed to produce ozone come from automobile exhaust. Ozone formation occurs most often during the early midday, and begins to decrease during late afternoon and evening. Symptoms from exposure to low concentrations of ozone include eye, nose, throat, and lung irritation. These symptoms can be seen after only about 10 to 30 minutes of exposure. At higher concentrations, coughing and breathing problems occur. Even higher concentrations result in chest pain and pneumonia. People who suffer from lung diseases such as asthma and emphysema are more sensitive to lower levels of ozone.

Nitrogen Oxides (Nox) come in the following forms: nitric oxide (NO), which is a colorless gas; nitrogen dioxide (NO2), a reddishbrown or dark orange gas; nitrogen trioxide (N2O3), a colorless gas; nitrogen tetroxide (N2O4), a colorless gas; nitrogen pentoxide (N2O5), and nitrous oxide (N2O), which is colorless and often referred to as "laughing gas"(1,2) Reports estimate that about 300,000 tons of NOx are produced each year from industrial processes; combustion of fossil fuels (coal, oil) adds 10 million tons to that number (1). Nitrogen oxides are produced from many sources, such as burning of fuels in furnaces and internal combustion engines, detonation of explosives, welding, and tobacco smoke. Diesel exhaust may contain nitric oxide, while cigarette smoke also contains nitrogen oxides. The

most common forms of nitrogen oxides in the air are nitric oxide and nitrogen dioxide. Nitrogen dioxide, which gives smog its brown color, can be detected by its odor or taste at low concentrations. Symptoms of exposure include coughing, difficulty in breathing, chest pain, fluid build-up in the lung, irregular heartbeat, and eye irritation (2). In some people, only labored breathing and coughing may develop at first, and then the symptoms subside. A few weeks later, people may enter a second stage, characterized by fever, chills, and fluid in the lungs. Death may occur in either of the two stages, depending on the severity of the effects and the health of the individual.

Particulates come from a number of sources, including automobile emissions, smokestacks, or blowing dust. The particles may be large enough to be seen by the naked eye, or they may be extremely small. The size is important in determining the effect of the particle on the respiratory system. Smaller particles may pose the greatest threat. For example, asbestos fibers are capable of causing cancer, silica particles may cause a disease called silicosis, and coal dust may cause pneumoconiosis. The composition of the particulates is also important. Heavy metals, such as lead, cadmium, and others are often found in the particulate material (1).

2.

III.

Heavy Metals
Heavy metals are everywhere in nature as components of the earth's crust. Plants can absorb and accumulate metals, which may be toxic. Industrial development has resulted in exposure to heavy metals in people because of increased production of by-products such as cadmium, mercury, chromium, and zinc. Due to both the prevalence, relative toxicity, and the disproportionate exposure impact on poor and undeserved communities, this module will describe the relative toxicity and health impacts from four of the most toxic heavy metals: arsenic, cadmium, lead, and mercury.

Arsenic, one of the most toxic metals, is produced at a rate of about 60,000 tons per year. It is found primarily in a trivalent form or a pentavalent form (2). The pentavalent form is not as toxic as the trivalent form, and will not be discussed further here. The trivalent form of arsenic is the most toxic and it is deposited primarily in the respiratory tract. Excretion is primarily via the

urine, although excretion may also occur by the natural shedding of the skin and through sweat. Potable water usually has a very small arsenic concentration. It is also present in very small amounts in such things as wine and seafood. This is why the diet should be taken into account when determining arsenic exposure. The primary routes of exposure to arsenic are ingestion and inhalation. Arsenic tends to collect in skin, hair, and nails. It is removed mainly through the urine, a few days after it is ingested. This can result in some upset stomach. Measuring arsenic in the urine is the main way to detect arsenic exposure. Acute exposure to arsenic may result in death, fever, anorexia, and liver enlargement (2). Chronic exposure may result in poisoning of the nervous system, liver damage, and peripheral vascular disease, which could result in gangrene of the lower limbs. This condition is more commonly known as "black foot disease" and was a phenomenon that occurred in Taiwan from arsenic contamination of the drinking water supply. In addition, skin cancer and lung cancer may result from chronic arsenic exposure. Chronic arsenic exposure has also been associated with leukemia, kidney, and bladder cancers, dermatitis, hyper pigmentation, and keratosis (or arsenical keratosis). Approximately 900,000 workers in the United States may be occupationally exposed to arsenic fumes and dust such as in smelting industries. The major source of occupational exposures to arsenic in the United States is in industries involved in the manufacture of pesticides, herbicides, and other agricultural products.

Cadmium is a byproduct of the mining and smelting of lead and zinc.(2). It does not corrode and is primarily used for electroplating activities. Cadmium can gather and concentrate in plants. It has also contaminated irrigation waters and is found in fertilizers. Shellfish represent a major source of cadmium in the diet (1001,000 microgram per kilogram [ g/kg]). Cadmium is also found in tobacco, each cigarette has approximately 1-2 g of cadmium. Approximately 1 g of cadmium may be found in one liter of breast milk. Very little cadmium is absorbed through the ingestion route, and it is not easily absorbed. Acute toxicity from cadmium exposure occurs primarily through ingestion of contaminated beverages or food. This could result in nausea, vomiting, and abdominal pain. Acute toxicity through

inhalation may result in chemical pneumonia and fluid in the lung. Irritation of the nose and throat, coughing, dizziness, weakness, chills, fever, chest pains, and labored breathing are also symptoms. Acute cadmium toxicity through inhalation may result in a condition known as metal fume fever. Chronic toxicity may result in chronic obstructive pulmonary disease, emphysema, and kidney disease. It may also result in adverse affects to the cardiovascular system and the skeleton (1,2).

Lead is primarily used in the manufacture of batteries, plastics, china, ceramic glass, and paint products. It is the most widespread toxic metal on earth and is the second most hazardous substance found at sites listed on the National Priorities List (NPL). Scientific evidence links exposure to lead and adverse health effects due to acute and chronic exposure to lead. The primary route of lead exposure is ingestion. This could occur through eating lead-based paint flakes and chips (e.g., pica-like behavior), breathing contaminated dust, drinking contaminated water, and absorbing lead from lead-contaminated glaze in pottery. Children are particularly at risk. Approximately 35% of U.S. black children have blood lead levels greater than 10 g/L (13). Blood lead levels are consistently higher for poor and minority children and for residents of largely urban areas. The fetal brain may be particularly sensitive to the toxic effects of lead because of the immaturity of the blood-brain barrier in the fetus. The toxic effects of lead include lead encephalopathy (brain disease) in children, resulting in lethargy, vomiting, irritability, loss of appetite, and dizziness (1,2). In adults, lead causes high blood pressure, and adverse reproductive effects (lowered sperm count and sperm motility). One classic symptom of lead toxicity are the Burton's lines, which are purple-blue discolorations of the gums (1,2). The primary measure for treating lead toxicity is through chelation therapy (binding of lead with other metals to remove it from the body).

Mercury is the third most toxic substance in the environment (1,2). Approximately half of all mercury is used to produce vapor lamps, fluorescent tubes, thermometers, and electrical products. It exists in a number of forms, which may affect different parts of the body. Organic mercury primarily affects the brain. Methyl mercury is the most toxicological form of the element and, by its accumulation in the central nervous system (CNS), may result in neurotoxic effects in adults and toxicity in the fetuses of mothers exposed to methyl mercury during pregnancy. Metallic mercury is slowly absorbed by

the gastrointestinal system and is not as toxic as methyl mercury (14). Inorganic mercury (mercury salts) primarily affects the kidneys. Exposure to mercuric salts may lead to abdominal cramps and bloody diarrhea. Chronic mercury exposure may lead to tremor and personality disturbances and permanent CNS damage may result from methyl mercury exposure. Acute mercury exposure can be assessed by measuring the level of mercury in blood. Chronic exposure is best assessed by measuring the amount of mercury in urine (1,2). Chelation therapy is typically used in acute mercury poisoning. A classic epidemiological study of mercury exposure involves the occurrence of Minamata disease. Minamata disease results from methyl mercury poisoning and leads to a neurological disorder. Methyl mercury bioaccumulates in fish and shellfish. Thus, exposure to humans primarily occurred through consumption of methyl mercurycontaminated shellfish and fish from Minamata Bay.
o o

IV.

Benzene
Benzene is a component and a by-product of gasoline. Benzene is widespread in the environment, and is one of the most prevalent solvents. In addition, it has been used as a solvent in rubber, inks, adhesives, and transformer fluids (1,2). Benzene dissolves easily in the bloodstream and quickly diffuses from the lungs to the blood and is metabolized in the liver to compounds that interact with cellular DNA. In addition, it is lipid-soluble and is easily absorbed by the skin and by cells lining the digestive tract. Inhalation is the predominant route of exposure to the toxic effects of benzene, particularly in the workplace. Acute exposure to benzene may result in CNS effects, which may lead to unconsciousness and death. There is no antidote for acute benzene poisoning. Chronic benzene exposure may result in bone marrow damage, resulting in anemia. Symptoms of chronic benzene exposure may include fatigue and anorexia. Leukemia is a classic outcome from chronic low-level exposure to benzene with a latency period of about 15 years.

V.

Polychlorinated Biphenyls (PCBs)

PCBs are another major contaminant of concern in communities (13). They were used in plasticizers, adhesives, and as dielectric fluids in capacitors. In humans,

they accumulate in fat tissue and milk, which is a major route of excretion (1,2). PCBs cause liver cancer in rats and mice and is classified as a probable carcinogen in humans by EPA. PCBs are persistent in the environment and bioaccumulate upward in the food chain. A non-occupational source of PCBs is in fish from contaminated water. Cultures where subsistence fishing is a primary source of food would subsequently represent populations of concern regarding PCB-contaminated fish (15). High-level exposure to PCBs may cause a classic dermatological condition called chloracne. Developmental and fetotoxic effects may also be observed in humans. Occupational exposures to PCBs primarily occurs in the production of electrical equipment. Since 1977, PCBs have been banned from further production as a material for the production of electrical equipment and chronic workplace exposure is now uncommon.

VI.

Pesticides
Several classes of pesticides cause adverse human health effects in humans. These major classes of pesticides include insecticides, herbicides, fungicides, fumigants, and rodenticides. Seasonal agricultural workers have an increased risk of harmful human health effects due to pesticide exposure (16).

Insecticides include the organochlorides, organophosphates, and the carbamates. Organochloride insecticides affect the peripheral nervous system (PNS) through dermal absorption, inhalation, and ingestion. Organochloride compounds also decrease antibody production, placing a person at risk for infection (1,2). DDT is a organochloride insecticide that persists and bioaccumulates in the environment, which is why it is no longer manufactured as a pesticide. Organophosphorous exposure may result in headache, anxiety, chest tightness, seizures, loss of consciousness, abnormal heart beat, and liver dysfunction (1,2). In addition, Organophosphorous pesticides, like malathion, seem to enhance the immune response in some circumstances. Parathion has been known to decrease antibody production. Trainers may want to discuss the use of insecticides. Ask participants about their insecticide use, listing types and determining their knowledge of the contents of these substances.

Herbicides such as 2,4,5-T, 2,4,-D, and the classic contaminant, 2,3,7,8 TCDD (dioxin) are toxic to both animals and humans (1,4). Liver problems and nerve damage may result from chronic herbicide exposure, while chloracne is a classic symptom of herbicide dermal exposure. Fungicides are used in the treatment of fruit trees and vegetables and have a relatively low toxicity (2). Skin irritation, headache, nausea, vomiting,

lethargy, and dermatitis are classic symptoms of some fungicides, such as creosote and hexachlorobenzene. Fumigants are used to eradicate insects, bacteria, and rodents. Fumigants are typically used on fruits, vegetables, ships, and buildings (1). Methyl bromide is a classic fumigant that may result in dermatitis, pulmonary irritation, headache, nausea, vomiting, dizziness, and dementia from exposure via inhalation and dermal exposure. The trainer may want to discuss the use of fungicides and fumigants in the home (home gardens, etc.).

Rodenticides are used primarily to eradicate rats, mice, rabbits, and gophers (1,2). Warfarin is a rodenticide that causes severe adverse health effects. Participants may list the types of chemicals they use in the removal of pests. Determine through discussion, whether any adverse health effects have been seen.

VII.

Radiation and Radioactive Materials

The two major classes of radiation are ionizing radiation and non-ionizing radiation. Ionizing radiation affects the bone marrow, resulting in a decrease in red blood cell production, reddening of the skin, gastrointestinal and reproductive effects, cataracts, birth defects, and respiratory illness (1,2). Non-ionizing radiation is associated with mutagenic and carcinogenic effects, primarily by UV radiation, which can alter the repair mechanisms for DNA and potentially lead to skin cancer. The exposure of radium dial workers in the United States is the most classic epidemiological case of occupational radiation exposure. Ingestion of radium may result in bone cancer. Atom bomb survivors were also the victims of radiation exposure, as well as underground miners exposed to radon, patients irradiated with x-rays for ankylosing spondylitis, and children irradiated with x-rays for ringworm (1,2). In addition, radiation is associated with skin, thyroid, and lung cancers, particularly among uranium mine workers.