In the context of this text, risk assessment is the process of determining the likelihood of toxicity for an individual or group after a perceived exposure to some substance, generally referred to as a xenobiotic. It involves determining the nature and extent of the exposure (ie, xenobiotic, dose, duration, route) and its specific clinical effects, defining an exposure pathway, and assessing the likelihood of effects from a given situation. A published body of knowledge can be applied to some components of risk characterization or assessment. An overview and a number of tools can be accessed through the Web sites of the US Environmental Protection Agency (EPA) and the Agency for Toxic Substance and Disease Registry (ATSDR) of the Centers for Disease Control and Prevention (CDC).1,9 However, any given risk assessment is often based on incomplete information. This may include such features as uncertainty regarding the exposure xenobiotic or mixture, whether there has been an actual exposure or just proximity to the xenobiotic (completion of an exposure pathway), lack of the exact dose, or unpredictable features such as host factors (underlying medical conditions or genetic polymorphisms) that could modify the response to a potential exposure. Unfortunately, those conducting a risk assessment are affected by their own biases and assumptions in the interpretation of their results, as are the people to whom a risk assessment is communicated. The emotional response to being “poisoned” makes evaluation and attribution even more difficult.
A good example of the practical difficulties involved in a risk assessment is evident from a published description of mass psychogenic illness.18 In this incident, many individuals at a school complained of odor-triggered symptoms that spread in a so-called “line of sight” transmission with no evident dose–response pattern. Extensive testing identified the possibility of potential sources of exposure, such as dry floor drain traps. However, no actual release was documented, nor was a scenario that would present significant harm identified. Yet symptoms recurred when people returned to the school. This is considered an example of psychogenic illness. The extent of investigation of these events can be profound, highlighting the difficulty in appropriately applying potentially unlimited laboratory technology to a situation. In addition, our ability to assess a “no-risk” situation is limited, as can be noted in the letters to the editor of the journal in which the article was published criticizing the methods or conclusions in this event and “subsequent and comparable” outbreaks.4,16,23
The response of individuals to uncertainty correlates with their affinity for one component of the negative data paradigm—“the absence of evidence of harm” versus “evidence of absence of harm.” Both of these positions should have at their core the continued evaluation of evidence as it becomes available, with subsequent refinement of a resulting risk assessment. Unfortunately, these potentially converging points on a spectrum of knowledge and research have been polarized in debate and policy as two opposing principles: the Kehoe Principle and the Precautionary Principle. The Kehoe Principle is best summarized as “prove something is harmful before excluding a product with known benefits because of concern about potential, unproven future adverse effects.” A common example of the use of this principle is the continued marketing of a xenobiotic after another member of the class has been removed because of safety issues. More intense scrutiny may be indicated, but a class-wide medication recall without evidence of some level of harm by an individual therapeutic drug is very rare. This principle has been misused in the past to minimize known risks attributable to environmental lead pollution to delay removal of lead additives from gasoline.26 Critics of the Kehoe Principle have suggested that waiting for evidence of harm from a substance results in costly or irreparable damage.
The alternative position of the Precautionary Principle is often summarized as “where there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason to postpone cost effective measures to prevent environmental degradation.”21,30 Critics of the Precautionary Principle often cite the lack of attention paid to the “cost” component of the principle, complaining that devotees stifle economic growth and prosperity with unfounded fears rather than reasoned consideration of known data. This principle is commonly extended to potentially harmful situations other than the environment. A common criticism of the Precautionary Principle is the degree to which alternative actions have been evaluated for safety. As an example, concern about thimerosal safety (as a vaccine preservative and source of ethylmercury exposure) in young children led many parents to forego childhood vaccinations. Vaccine manufacturers have removed the thimerosal preservative from most routine childhood vaccines. Although this process was accelerated by the theoretical—and, ultimately, unfounded—concerns regarding this source of mercury exposure in young children, the cost of delayed or omitted vaccination was a number of real and preventable infectious diseases that occurred, including hepatitis B.5,6,11
Although the Kehoe and Precautionary Principles originated as policy approaches to public health issues, they underlie the automatic or subconscious biases that each individual brings to his or her own personal risk assessment or tolerance. The response to uncertain situations is derived from one’s framing of belief systems and assumptions about life, justice, and eternity.3,10,14 These underlying world views should be explicitly recognized and addressed in a formal risk assessment. Table 130–1 lists the components of a risk assessment.
TABLE 130–1.Components of Risk Assessment ||Download (.pdf) TABLE 130–1. Components of Risk Assessment
|Hazard Identification |
|Name and amount of suspected xenobiotic (or general use category if the xenobiotic is unknown) |
|Exposure Pathway |
|Proposed route of exposure |
|Consistency with the nature of the xenobiotic (eg, water-soluble liquid) |
|Modifying Factors |
|Environmental factors that would influence systemic availability of the xenobiotic |
|Patient characteristics (susceptibility or resistance factors), such as: |
|Chronic medical conditions |
|Possible xenobiotic–drug or other interactions |
|Genetic polymorphisms in hepatic or other metabolic pathways |
|Toxicity Assessment |
|Compare and contrast organ effects expected from the particular xenobiotic with existing symptoms |