Page 51 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

18 SECTION | I General

VetBooks.ir periods of time causing tumors in rodents. The exposure ways to organize and synthesize the knowledge base that
we call veterinary toxicology. One dimension is the vari-
response relationship for cell killing may likely have a
ous classes of toxicants. Another dimension of the field
threshold that must be considered in extrapolating the
findings from high-exposure level studies in rodents to relates to the media that contains the toxicant: air, water,
humans exposed to low concentrations of these chemicals. soil, and feed. Another dimension considers the various
Readers interested in a contemporary view of the use of routes of exposure of toxicants: inhalation, ingestion, der-
mode of action information to improve regulatory mal, or purposeful injection. It is also convenient to con-
decision-making will be interested in a summary paper by sider the various organ systems and processes that may be
Carmichael et al. (2011). The NRC (2011) has also affected by toxicants. This is the basis for organization
addressed this issue in offering advice on the US of a major section in this book. It is also important to
Environmental Protection Agency draft IRIS assessment consider the individual toxicants or classes of toxicants.
of formaldehyde. Rhomberg et al. (2011b,c) also This approach is used in organizing another major section
addressed issues involving the EPA’s formaldehyde of this book. Finally, veterinary toxicologists recognize the
assessment. necessity of considering the various species of concern.
More recently, enthusiasm has developed for the con- Increasing veterinary medical practitioners have become
cept of “Adverse Outcome Pathway” (AOP) analysis. The more specialized with many focusing their clinical skills
AOP approach focuses on developing information on the on a single species. This book does not include a section
pathobiological pathway by which a critical adverse effect addressing the toxicology of individual species. To have
is observed with a particular chemical. Information done so would have substantially increased the size of this
obtained on detailed investigation of this pathway can text. However, chapter authors have endeavored to discuss
then be used to inform regulatory decisions on the nature species variations in responses to toxic agents. It is note-
of the exposure-dose-response relationships to be consid- worthy that several textbooks, that of Peterson and Talcott
ered in limiting human exposures. (2012) and Poppenga and Gwaltney-Brant (2011),focus
It is my contention that understanding the basic con- on small animals. Some of the major comprehensive
cepts conveyed in Figs. 1.1, 1.2, and 1.4 can be very use- veterinary medicine texts, such as the Current Veterinary
ful in investigating a range of situations where the Therapy series, that focus on other species include chapters
objective is to establish or refute a causal association on toxicology related to that species.
between a given source and toxic agent and an increased
incidence of an adverse health outcome. The term,
increased incidence, is used advisably recognizing in SOURCES OF INFORMATION
most situations involving domestic animals, either as Case Observations in the Species of Interest
commercial herds or as companion animals, the situation
is one of presence or absence of a given disease and the There are multiple sources of scientific information for
“ruling out” of other differential diagnoses. However, in characterizing the relationship between exposure to a toxi-
situations involving human populations and in experimen- cant and toxicant-induced response. Fig. 1.6 is a schematic
tal studies in animals, the issue frequently encountered is rendering of the multiple sources of information that may
whether a given toxicant exposure has caused an increase be used to understand the toxicity of a given agent.
in a disease recognizing that most diseases may have mul- As discussed earlier, the origins of veterinary toxicol-
tiple etiologies, e.g., cancer, hypertension, and diabetes. ogy and toxicology in general are both rooted in observa-
This is especially the case in evaluating diseases that typi- tions. An adverse health effect, either a pattern of
cally occur late in life, such as cancer and chronic dis- morbidity or mortality in an individual or population, is
eases, and with exposure to toxicants that may occur at observed and the disease linked to exposure to a toxicant.
low levels over long periods of time. In some cases, such In many instances, the time interval between exposure
as lung cancer and cardiorespiratory disease in humans, a and the adverse health outcome was brief, which aided in
risk factor such as cigarette smoking may cause effects deducing an association. Because the causal association
that are so substantial it is a challenge to determine if any was identified in the species of interest, whether it be a
concurrent low-level exposure to other toxicants, such as person, a horse, a cow, or a dog, it was not necessary to
air pollutants, are having chronic effects at low exposure extrapolate between species. Nor was it necessary to
concentrations. explore in-depth the mechanistic basis for the causal
association to either diagnose a particular case or prevent
future cases. Action to prevent exposures and, thus,
Veterinary Toxicology Is Multifaceted
prevent disease, could be based on empirical observations.
It will be apparent to the reader of this book that veteri- As you read many of the chapters in this book,
nary toxicology is multifaceted. Thus, there are many you will note that details of the mechanism by which