Page 42 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Concepts in Veterinary Toxicology Chapter | 1 9

VetBooks.ir funders. Hundreds of scientists who gained valuable expe- the risk analysis paradigm and the use of scientific knowl-
edge to inform regulatory actions (McClellan, 1999,
rience as students, postdoctoral fellows, or staff members
at the Institute became leaders in the field. This included
2010, 2014; McClellan et al., 2012). The development of
dozens of veterinarians. risk analysis as a specialized area of interdisciplinary sci-
In the late 20th century, the Food and Drug ence led to the founding of the Society for Risk Analysis
Administration (FDA) continued its traditional dual in 1981 of which I was a charter member and later named
emphasis of ensuring both the efficacy and the safety of a Fellow. The risk analysis paradigm originally proposed
drugs and medical devices continued. Increased emphasis by the National Research Council (1983) and used by the
has been given by the FDA in recent decades to veteri- USEPA is shown in Fig. 1.2. A later report, Science and
nary drugs and to the potential for veterinary drugs to Judgment in Risk Assessment (NRC, 1994; McClellan,
contaminate meat and milk. 1994), and reports from the Risk Commission (1997),
Increasing public concern for safety/risk and the reaffirmed use of the risk paradigm that continues to be a
resulting legislation led to the development of increas- cornerstone of activities not just at the EPA but in other
ingly formalized approaches to both safety and risk analy- national and international agencies and in the private
sis. This included more clearly defined roles for using the sector concerned with human health.
results of toxicological studies, including studies with lab- The original key elements of the risk paradigm were
oratory animals, to assess the safety, or conversely risk, to (1) hazard identification, (2) exposure response assess-
humans of the use of pharmaceuticals, other products in ment, (3) exposure assessment, and (4) risk assessment.
commerce, and existing and new technologies. In my The NRC (1994) report emphasized the importance of a
opinion, the same scientific knowledge base can be used fifth element: using the results of the risk analysis to
to address concerns for safety and risk. Scientific informa- guide future research and, thus, reduce uncertainty in
tion can be used to inform regulatory and other societal future risk estimates. In addition, I have added a sixth
actions that maximize safety and minimize risk, both are over-arching element: risk communication. The hazard
relative not absolute. identification element has been a source of contention
and confusion both with the public and in the scientific
community, especially with regard to cancer, as I will
Toxicology Joined to the Risk Paradigm
discuss later.
As noted earlier, federal legislation passed in the 1970s Hazard is defined as the potential for an agent under
focused on health impacts of environmental and occupa- some conditions of exposure to cause an adverse effect
tional exposures and led to more formalized approaches (NRC, 1983, 1994; McClellan, 1999, 2010, 2014). With
to evaluating the risks and safety of various exposures. this definition the level of exposure or dose required
The risk paradigm built on the long-standing paradigm of to produce an adverse health effect is not considered.
linking sources of dose exposure to adverse health out- An agent may be classified as a hazard irrespective of
comes that had guided toxicology from its earliest days whether or not the exposure conditions required to elicit
(Fig. 1.1). I have reviewed elsewhere the development of adverse health effects under experimental conditions are

Sources of Dose to Health
potential toxicants Exposure biological target responses

Industrial activities Mechanisms Presence of Mechanisms Dose at multiple Mechanisms Acute to chronic
Consumer products influencing toxicant influencing levels from critical leading to responses including
Agricultural practices transport via in different absorption, macromolecular alterations in both functional
Forage multiple media, air, distribution, to tissues to total function and effects and cancer
Feed pathways water, food metabolism body structure
and excretion

Exposure assessment Toxicokinetics Toxicodynamics

Characterization of hazard and exposure–response relationships

Risk characterization
FIGURE 1.1 Critical linkages for integrating information from sources of toxicants to the development of adverse health effects.