Principles and Practice of Toxicology in

Public Health 2nd Edition, (Ebook PDF)

Visit to download the full and correct content document:
https://ebookmass.com/product/principles-and-practice-of-toxicology-in-public-health-
2nd-edition-ebook-pdf/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...

Community and Public Health Nursing: Evidence for

Practice 2nd Edition, (Ebook PDF)

https://ebookmass.com/product/community-and-public-health-
nursing-evidence-for-practice-2nd-edition-ebook-pdf/

Essentials of Public Health Preparedness and Emergency

Management (Essential Public Health) 2nd Edition,
(Ebook PDF)

https://ebookmass.com/product/essentials-of-public-health-
preparedness-and-emergency-management-essential-public-
health-2nd-edition-ebook-pdf/

The Principles and Practice of Yoga in Health Care 1st

Edition, (Ebook PDF)

https://ebookmass.com/product/the-principles-and-practice-of-
yoga-in-health-care-1st-edition-ebook-pdf/

Cosmetic Dermatology: Principles and Practice, Second

Edition: Principles & Practice 2nd Edition, (Ebook PDF)

https://ebookmass.com/product/cosmetic-dermatology-principles-
and-practice-second-edition-principles-practice-2nd-edition-
ebook-pdf/
Social and Behavioral Foundations of Public Health 2nd
Edition, (Ebook PDF)

https://ebookmass.com/product/social-and-behavioral-foundations-
of-public-health-2nd-edition-ebook-pdf/

Community/Public Health Nursing Practice E Book: Health

for Families and Populations (Maurer, Community/ Public
Health Nursing Practice) 5th Edition, (Ebook PDF)

https://ebookmass.com/product/community-public-health-nursing-
practice-e-book-health-for-families-and-populations-maurer-
community-public-health-nursing-practice-5th-edition-ebook-pdf/

Essentials of Management and Leadership in Public

Health (Essential Public Health) 1st Edition, (Ebook
PDF)

https://ebookmass.com/product/essentials-of-management-and-
leadership-in-public-health-essential-public-health-1st-edition-
ebook-pdf/

Health Behavior Theory for Public Health 2nd Edition,

(Ebook PDF)

https://ebookmass.com/product/health-behavior-theory-for-public-
health-2nd-edition-ebook-pdf/

Evaluating Public and Community Health Programs 2nd

Edition, (Ebook PDF)

https://ebookmass.com/product/evaluating-public-and-community-
health-programs-2nd-edition-ebook-pdf/
 Chapter 3
Toxicity and the Factors That Modify Toxic Responses
Cellular Basis of Toxicity
Spectrum of Adverse Effects
Factors That Modify Toxicity
Toxicogenomics and Its Importance in Public Health
Bibliography
Chapter 4
Biological Poisons: Plant and Animal Toxins
Introduction
Bacterial Toxins
Fungal Toxins
Algal Toxins
Higher Plant Toxins
Animal Toxins
Bibliography
Chapter 5
Environmental Pollutants and Their Fate
Introduction
Unfortunate Lessons Learned
Pollution Versus Contamination
Environmental Chemistry
The Environment: Compartments and Ecosystems
Toxicity in a Population
Endocrine-Disrupting Compounds
Conclusion
Bibliography
SECTION II TOXICOLOGY PRINCIPLES
Chapter 6
Dose and Response
Introduction
Relating Dose to Response
Dose–Response Graphs
How Individuals May Respond in a Population
The Dose Must Be Referenced to Time
Dose Standardization Based on Body Weight
Toxicity Rating
Referencing Dose to Environmental Media
Bibliography
Chapter 7
Absorption of Toxicants and Models of Disposition
Toxicant Entry into the Body
Cell Membranes
Movement of Toxicants Across Cell Membranes
Skin Absorption
Gastrointestinal Absorption
Respiratory Absorption
Other Exposure Routes
Chemical Disposition and Toxicokinetics
Models of Disposition
Bibliography
Chapter 8
Distribution, Storage, and Elimination of Toxicants
Introduction
Body Water and Volume of Distribution
Plasma Binding, Blood Flow, and Barriers to Distribution
Toxicant Storage
Toxicant Elimination
Urinary Excretion
Fecal Elimination
Pulmonary Elimination
Minor Routes of Elimination
Bibliography
Chapter 9
 Biotransformation
Introduction
Enzymes
Tissues Where Biotransformation Proceeds
Phase 1 Reactions and Cytochrome P450
Phase 2 Reactions
Bibliography
Chapter 10
Chemical-Induced Mutagenesis
DNA and Mutations
Mutations and Apoptosis
Tests for DNA Damage and Mutagenicity
Examples of Chemical Mutagens
Bibliography
Chapter 11
Chemicals and Cancer
Introduction
Mutations in Genes That Regulate Cell Growth and
Differentiation
Oncogenes
History of Chemical Carcinogenesis
Characteristics of Cancer Cells
Benign and Malignant Tumors
Tumor Angiogenesis, Metastasis, and Staging
Classification Systems for Carcinogens by Agency
Carcinogen Classification
Exposure to Carcinogens
Chemical-Induced Carcinogenesis Is a Multistep Process
Informing the Public About Carcinogens
Bibliography
SECTION III SYSTEMIC TOXICITY
Chapter 12
The Role of the Immune System
Introduction
Chemical Exposures
Immune Responses
Organs of the Immune System
Cells of the Immune System
Antibodies
Immunological Disorders
Immunosuppression by Toxicants
Examples of Chemical-Induced Immunological Disorders
Experimental Immunological Testing
Bibliography
Chapter 13
Skin
Introduction
Structure of the Skin
Skin Absorption of Chemicals
Skin Toxicity: Local Effects
Bibliography
Chapter 14
The Liver and Kidneys
The Liver
The Kidneys
Bibliography
Chapter 15
The Cardiovascular System
General Considerations
Cardiac Physiology
Cell Types
Cardiac Electrophysiology
Assessing Cardiac Function
Effects of Toxicants on the Cardiovascular System
 Blood Vessels
Blood
Bibliography
Chapter 16
The Respiratory System
General Considerations
Nomenclature of Airborne Toxicants
Functional Divisions of the Respiratory System
Respiratory System Injury
Exposures to Air Pollutants
Defense Strategies
Types of Injury
Bibliography
Chapter 17
The Nervous System
General Considerations
Cells of the Nervous System
The Blood–Brain Barrier
Neuron Action Potential and Synaptic Function
Neurotoxicity
Bibliography
Chapter 18
The Endocrine System
General Considerations
The Parts of the Endocrine System
The Reproductive System
Bibliography
SECTION IV TOXICOLOGY PRACTICE
Chapter 19
The Practice of Toxicology
Introduction
Categories of Toxicologists
Expectations and Requirements for Toxicologists
Toxicologists as Expert Witnesses
Websites
Bibliography
Chapter 20
Regulatory Considerations
Standards, Guidelines, and Regulatory Agencies
Public Awareness and Public Outrage
Regulatory and Nonregulatory Agencies: Their Role in
Protecting the Public from Chemical Exposures
Industrial Versus Environmental Standards
The Agency for Toxic Substances and Disease Registry
The National Toxicology Program
Consumer Product Safety Commission
Websites
Bibliography
Chapter 21
Toxicity Testing
The Nature and Scope of Toxicity Testing
Toxicity Test Objectives and Considerations
Animal Use and Extrapolation to Humans
Practical Aspects of Measuring Toxicity Experimentally
Acute Local Toxicity: Tests for Irritancy and Corrosiveness
Acute Systemic Toxicity: Use and Limitations of LD50
Efficacy, Toxicity, and Lethality
Other Examples of Prechronic Toxicity Testing in
Laboratory Animals
Chronic Toxicity Testing in Laboratory Animals
Human Studies
Alternative Toxicity Testing Methods
Examples of In Vitro Tests for Several Toxicological
Endpoints
Conclusion
Websites
Bibliography
Appendix 21-1: Example of a Template for a Subchronic
Toxicity Study in Rodents for FDA Review
Chapter 22
Uses and Limitations of Product Labeling for Public
Safety
The Purpose of Product Labeling
Use of Product Labels by Consumers
Limitations of Product Labels
Federal Requirements
FIFRA and Pesticides
Pesticide Product Labeling
Product Labels Are Not Material Safety Data Sheets
Federal Food and Drug Administration Requirements for
Labeling
Websites
Chapter 23
Toxicology Principles in the Management of Acute
Poisonings
Introduction
Management of Acute Poisoning
Route of Exposure Influences Toxicity: An Example Using
Cocaine
Intentional and Unintentional Exposures in the American
Population
Inhalant Use
Toxicities Associated with “Street Drugs”
Websites
Bibliography
Chapter 24
Risk Assessment and the Perception of Risk
Overview of Risk
Risk Assessment
Cancer Risk Assessment
Ecological Risk Assessment
Toxicant Interaction and Chemical Mixtures
Responding to Public Concerns
Websites
Bibliography
Chapter 25
Making Informed Decisions
Difficulties in Decision Making
Risk Assessment in the Federal Government: Managing the
Process
Making the Best Decisions
The CRAM Report
Websites
Bibliography

Glossary of Terms
Index
 Preface

Toxicology deals with the harmful effects that can potentially result from
exposures to chemical agents in humans and other organisms. Before 1970,
there were virtually no academic programs of study in toxicology. Today,
there are hundreds of colleges and universities that offer programs at the
bachelor’s level through the doctoral level, providing the requisite education
for the student of toxicology. Recognition of the important role that the
discipline plays in the protection of health and the environment has also led
to the development of programs in the interdisciplinary academic setting that
are geared toward students at schools and colleges of public health. Such
beginning courses in toxicology are typically offered at the graduate level and
attended by individuals with interests as diverse as environmental health,
industrial hygiene, epidemiology, biostatistics, medicine, nursing, law,
engineering, biology, and chemistry, as well as toxicology. Clearly, this is a
very heterogeneous population of students, all viewing the practice of public
health and public health issues from different perspectives.
Although the study of toxicology at a level commensurate with earning a
graduate degree in this concentration may be beyond the scope of most
students of public health, we should recognize that most, and perhaps all,
public health students should be at least exposed to some of its content. The
content selected in Principles and Practice of Toxicology in Public Health,
Second Edition is intended to provide both groups of students with an
understanding of the nature and scope of the discipline. This is necessary to
participate in a meaningful way in the often highly visible problem-solving
and decision-making processes required of public health professionals.
Whether we are dealing with issues as diverse as a workers’ compensation
claim for a job-related exposure and injury or the removal of toxic wastes
from an urban community, we must be able to communicate with each other,
the public, and our political leaders concerning how chemicals can, and the
conditions under which they may, realistically produce harm. Understanding
is a requirement for establishing rational and better ways to protect and
manage individuals, populations, communities, and our environment from the
potentially harmful effects of chemical exposures. A required introduction to
the scope and content of toxicology for public health students should
therefore be viewed not as a punishment, but rather as an important part of a
general education.
Public health professionals working in municipal departments of public
health are generally very well informed about biological agents and perhaps
less informed about chemical exposures and toxicity. In our “preparedness”
for the general public, and especially in these troubled times, we recognize
that both biological and chemical agents constitute important concerns, and it
is anticipated that this text will provide some additional background and
information for you as well.
 Acknowledgments

The author wishes to acknowledge his family for their understanding and
enormous patience during the time of this writing. Thank you to Barbara,
Charles, Jeffrey, and Elizabeth for all of the hours that otherwise would have
been devoted to you. —I.R.
The author wishes to acknowledge Bobby, Jake, Shelby, Maya, and Logan
Bourgeois for their unwavering support. Without them, this would not have
been possible. —M.B.
 What’s New in the Second Edition

• Thoroughly updated with recent data and the latest information on topics
such as carcinogen classification, environmental chemistry, and bacterial,
plant, and animal toxins
• All new chapter on endocrine toxicology
• New “Case in Point” feature incorporating relevant current events and case
studies
• New “A Closer Look” feature with toxicological information
• New glossary terms, as well as clarification of toxic and hazardous
terminology
• New and updated tables and figures
 SECTION I

Introduction

CHAPTER 1
Toxicology and Its Roots as a Science

CHAPTER 2
Chemical Properties and Hazardous Chemicals Information
Resources

CHAPTER 3
Toxicity and the Factors That Modify
Toxic Responses

CHAPTER 4
Biological Poisons: Plant and Animal Toxins

CHAPTER 5
Environmental Pollutants and Their Fate
 CHAPTER 1

Toxicology and Its Roots as a Science

Introduction
It is clear that in our environments, we are routinely exposed to chemical
agents. We justify their use to maintain and improve our own well-being
and that of society in general. Unfortunately, we have seen, and may
continue to see, incidents of chemically induced adverse events in humans
and other species.
Bhopal, India, was the site of one of the largest industrial accidents of
the 20th century. In 1969, Union Carbide Corporation built a carbaryl
pesticide (trade name Sevin) factory there to support the emerging Indian
agricultural market. The production process used by the Union Carbide
India Limited (UCIL) plant combined methylamine with phosgene to form
methyl isocyanate (MIC), which was then added to 1-naphthol to generate
carbaryl. Poor economic conditions in India meant farmers were unable to
afford Sevin, and as a result, the factory had a large quantity of unsold
intermediates such as MIC in storage. In the early morning hours of
December 2, 1984, water entered an MIC tank and the resultant
exothermic reaction ruptured the tank and released more than 25 tons of
MIC vapor. Many of the plant’s safety features (flare towers, water
curtains, and vent scrubbers) had fallen into disrepair and failed to work.
Horribly, this accidental discharge of methyl isocyanate into the air
resulted in the overnight deaths of approximately 4,000 individuals, and
over 100,000 more sustained injuries, some of which were so severe that
many thousands later died. Prevailing winds carried the heavy gas over the
densely populated shanties of Bhopal. The citizens of Bhopal woke with
the onset of the initial effects of MIC exposure—coughing, air hunger,
 vomiting, and intense eye irritation. The primary cause of death was
pulmonary edema; many survivors showed signs of compromised
respiration (e.g., bronchoalveolar lesions and decreased lung function) and
impaired vision (e.g., loss of vision, loss of visual acuity, and cataracts).
Humans were not the only ones affected; thousands of animal carcasses
were collected in the weeks following the release.

Recognizing the benefits of chemicals in general, we accept the potential

risks related to their use until some undesirable event or additional
information about any particular chemical forces us to reevaluate its benefit
in light of the risk posed. As public health professionals, we further recognize
that, at times, large numbers of individuals may be exposed to certain
chemicals where there is often only limited information available about their
effects on human health. This is especially true for chronic “low level”
exposures. As we will see later, human safety is often inferred from
laboratory data in animals as the source of toxicity information as, for
example, in the case of satisfying the regulatory requirement for the safety of
a new food additive by the federal Food and Drug Administration (FDA).
A simple yet comprehensive definition of toxicology is the study of the
adverse effects of chemicals in biological systems. A biological system can
be as complex as an entire organism or can be a less complicated in vitro cell
culture system. As public health professionals, we direct most of our attention
to human health effects; however, we must also recognize that we share our
planet with other organisms, both plants and animals that are also affected by
chemical agents.
Paracelsus, a German-Swiss Renaissance physician (1493–1541),
expressed an early understanding of the conditions under which a chemical
can become harmful Paracelsus hypothesized that all substances are
potentially poisonous. The right dose differentiates a poison and a remedy.
While this statement shows clear recognition of the very basis of toxicity, the
dose, it further implies that concerns for a substance’s toxicity are also a
function of exposure, the conditions of exposure, the susceptibility of the
host, and other factors and circumstances that may have bearing on
evaluating the safety or hazard of a given exposure. All chemicals are toxic at
some dose and may produce harm if exposure is sufficient; all chemicals
produce their harm (toxicities) under prescribed conditions of dose or usage.
It has been said that there are no harmless substances, only harmless ways of
using them.
We must always remember that the evaluation of a chemical exposure as
harmless or hazardous should not be viewed only as a function of the
magnitude of the exposure (dose), or the types of toxicities that may produce
at some given dose.

Toxic Chemicals
Terms commonly used to refer to toxic chemicals are as follows:
• Toxic chemical
• Toxic substance
• Toxic agent
• Poison
• Toxin
• Toxicant
• Xenobiotic
Although the terms toxicant and toxin are frequently used interchangeably,
they have different meanings. A toxicant is any chemical that can potentially
produce harm. Toxicants may affect specific tissues or organs (target tissues,
target organs), such as benzene, which affects the blood and blood-forming
tissues. Toxicants may also be relatively nonspecific, thus affecting the entire
body. Sodium cyanide is an example of a systemic toxicant that has the
ability to interfere with all body cell utilization of oxygen. A toxicant may be
a heavy metal such as lead, a pesticide, an organic solvent, or even a toxin.
The term toxin, on the other hand, must be reserved for those chemicals that
are produced by living organisms. Rattlesnake venom or poisonous
mushrooms contain toxins. Many toxins are extremely hazardous chemicals
and can produce severe injury to tissues and organs, often to the extent that
death may result from body system failure (Table 1-1).
A poison is generally defined as any substance that when ingested,
inhaled, or absorbed or when applied to, injected into, or developed within
the body in relatively small amounts may, by its chemical action, cause death
or injury. A poison therefore could be any of the numerous synthetic
chemicals or a chemical produced by a living organism (toxin). The
commonly used term toxic substance does not describe whether one is
speaking about a particular chemical or a mixture of chemicals that
collectively have toxic properties. For example, whereas lead chloride is a
discrete chemical that has toxic properties, asbestos is not a discrete
chemical, but rather a mixture of various chemicals whose composition may
vary.

Table 1-1 Examples of Toxins

Toxin and Source Example of Tissue/System Affected
Aflatoxin B Liver Necrosis and Cancer
(Aspergillus flavus)
α-Amanitin Gastrointestinal Tract and Liver Cancer
(Amanita phalloides)
Anatoxin Nervous
(Anabaena spp.) (anticholinesterase)
Sodium fluoroacetate Cardiac, Skeletal Muscle, Nervous
(Dichapetalum cymosum)
Ochratoxin A Kidney
(Aspergillus ocraceus)
Pyrethrin I Nervous
(Pyrethrum cinariaefolium)
Tetrodotoxin Nervous
(puffer fish, amphibians)

Table 1-2 Examples of Xenobiotics

Toxicant and Source Example of Tissue/System Affected
Deltamethrin Nervous
(insecticide)
Ethylene glycol monomethylether Testis
 (solvent)
n-Hexane Nervous
(solvent)
Methyl isocyanate Lung and Eye
(used in insecticide manufacture)
1-methyl-4-phenyl-1,2,3,6- Nervous
tetrahydropyridine (MPTP)
(impurity in demerol)
Paraquat Lung
(herbicide)
Soman
Nervous
(nerve gas)

The term xenobiotic literally means foreign to the body and can refer to
any chemical that is not a natural component of the body (e.g., a synthetic
antibiotic). The term, however, is typically used in the context of any
synthetic chemical that has no beneficial effect on the body (Table 1-2).
The degree and nature of toxicity is not only related to which chemical
one is exposed (the hazard) but to the conditions of exposure as well (e.g., the
route and duration of exposure). For example, ethanol can acutely produce its
effects on the central nervous system, but over the long term it produces
chronic toxicity to the liver as well.
The practice of toxicology involves the application of toxicological
principles that are focused on environmental, regulatory, industrial, clinical,
or forensic issues, to name several. Indeed, any issue relating to health risks
from chemicals is of concern to toxicologists. Toxicology is an applied
science that has assimilated the theoretical and technical advances of
disciplines such as chemistry, biology, physiology, pharmacology, pathology,
epidemiology, and biostatistics. The duality of toxicology requires gathered
and applied science. For this reason toxicology is often described as a
“borrowing” science, and, indeed, this use of information from other
disciplines is one of toxicology’s greatest strengths. Toxicology can be
considered one of the most interdisciplinary sciences of the modern age.
Epidemiological Studies
In toxicology, proof that a given chemical exposure resulted in change(s) in
human health is established by a hierarchy of evidence. Students of public
health toxicology must further recognize the importance of epidemiology in
establishing toxicological causation. Epidemiological studies are considered
the highest level of scientific evidence for proving an association between a
particular chemical exposure and human health effects. Studies are conducted
using human populations to evaluate whether there is a causal relationship
between exposure to a substance and adverse health effects. These studies
can be based on literature that associates human illness with a particular
exposure, as well as toxicological evidence from studies in which animals
were exposed in a way that is likely to occur in humans. This scenario of
experimentally induced production of adverse effects or even death in
animals may or may not be similar to those effects that have been observed in
humans. There are a number of aspects in designing an epidemiology study,
the most critical being appropriate controls, adequate time span for the study,
and statistical ability to detect an effect. The statistical ability to detect an
effect should be based upon the study and control populations being as large
as possible. The risk to the exposed population must be compared to that in
an identical (e.g., same age, sex, race, economic status, etc.) unexposed
population. Many epidemiology studies evaluate the potential of a chemical
to cause cancer. Because most cancers have long latency periods (e.g., 20
years or more), the study must cover that period of time.
Types of epidemiological studies include:
• Cohort study—A cohort (group) of individuals with exposure to a
chemical and a cohort without exposure are followed over time to
compare disease occurrence.
• Prospective cohort study—Cohorts are identified based on current
exposures and followed into the future.
• Retrospective cohort study—Cohorts are identified based on past
exposure conditions and follow-up proceeds forward in time.
• Case control study—Individuals with a disease (e.g., cancer) are
compared to individuals without the disease to determine if there is an
association between the disease and prior exposure to an agent.
Another random document with
no related content on Scribd:
back
back
back
back
back
back
back
back
back
back
back
back
back
back
back
back
back