Lecture Notes
- Introduction to Toxicology (1)
- What is Toxicology?
- 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 (1.3MB)
- 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
- 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 (2,3-7,8-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 by-product
of industrial activities. If the second case is true,
such toxic substances are referred to as toxicants,
rather than toxins.
- 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.
- What is a Toxic Symptom? This term includes
any feeling or sign indicating the presence of a poison
in the system.
- 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.
- 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.
- 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
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.
- 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.
- 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."
- 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.
- 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.
- 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.
- Sub-disciplines of Toxicology
- The field of toxicology can be further divided into
the following sub-disciplines 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.
- The field of toxicology can be further divided into
the following sub-disciplines or sub-specialities:
- Classification of Toxic Agents (2):
Toxic substances are classified into the following:
- 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.
- 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.
- 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.
- 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. - 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.
- 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.
- 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.
- 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)
- Effect on target organs (liver, kidney, hematopoietic
system),
- General Classifications of Interest to Communities
- Air pollutants
- Occupation-related
- Acute and chronic poisons
- Air pollutants
- Heavy Metals
- 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 (2MB)
- 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. (36k)
- 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 (19k)
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:
- 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 DatabasesInformation on toxic chemicals is available at the following sites:
- 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).
- Region 1: Connecticut, Maine, Massachusetts, New Hampshire,
Rhode Island, Vermont
- Contact Information
Toxicology is the study of how natural or man-made poisons cause undesirable effects in living organisms.
« Presentation Outline | Test Your Knowledge Quiz »