PRINCIPLES OF TOXICOLOGY - Biology East Borneo

440 RISK ASSESSMENTcontrol population, but there are several problems in attempting to generalize the results of such studies.Exposure of a population is often difficult to quantify, and the extrapolation of observations from onesituation to another (e.g., different populations, different manners of exposure, different exposurelevels, different exposure durations) is challenging. For the most part, risk assessments for environmentalchemical exposures must rely on modeling and assumptions to generate estimates of potentialrisks. Because these risk estimates usually cannot be verified, they represent hypothetical or theoreticalrisks. This is an important facet of risk assessment that is often misunderstood by those who erroneouslyassume that risk estimates for environmental chemical exposure have a strong empirical basis.As discussed in subsequent sections, there are many sources of uncertainty in making risk estimates.Good data regarding chemical exposure and uptake are seldom available, forcing reliance on modelsand assumptions that may or may not be valid. Toxicity information often must be extrapolated fromone species to another (e.g., use of data from laboratory mice or rats for human health risk assessment),from one route of exposure to another (e.g., use of toxicity data following ingestion to evaluate risksfrom dermal exposure), and from high doses to the lower doses more commonly encountered withenvironmental exposure. In view of all of these uncertainties, it is impossible to develop preciseestimates of risks from chemical exposures. Choices made by the risk assessor, such as which exposuremodel to use or how to scale doses when extrapolating from rodents to humans, can have a profoundimpact on the risk estimate.Regulatory agencies address uncertainty in risk assessments by using conservative approaches andassumptions; that is, in the face of scientific uncertainty, they will select models and assumptions thattend to overestimate, rather than underestimate, risk so as to be health protective. Since most riskassessments are by, or for, regulatory agencies, this conservatism is a dominant theme in riskassessments and a continuous source of controversy. Some view the conservatism employed byregulatory agencies as excessive, resulting in gross overestimation of risks and unwarranted regulationsthat waste billions of dollars. Others question whether regulatory agencies are conservative enough,and suggest that the public (particularly more sensitive individuals such as children) may not beadequately protected by contemporary risk assessment approaches.Defining Risk Assessment ProblemsA coherent risk assessment requires a clear statement of the risk problem to be addressed. This shouldbe developed very early in the risk assessment process and is shaped by the question(s) the riskassessment is expected to answer. Ideally, both the risk assessor(s) and the individuals or organizationsthat will ultimately use the risk assessment will have input. This helps ensure that the analysis will betechnically sound and serve its intended purpose.One of the first issues to address is which chemicals or agents should be included in the analysis.In some situations this may be straightforward, such as a risk assessment focused specifically onoccupational exposure to a particular chemical. In other circumstances, the chemicals of concern maynot be obvious. An example of this would be risk assessment for a chemical disposal site where thechemicals present and their amounts are initially unknown. A related issue is which health effectsshould the risk assessment address. While it is tempting to answer “all of them,” it must be recognizedthat each chemical in a risk assessment is capable of producing a variety of adverse health effects, andthe dose–response relationships for these effects can vary substantially. Developing estimates of risksfor each of the possible adverse effects of each chemical of interest is usually impractical. A simplerapproach is to estimate risks for the health effect to which individuals are most sensitive, specifically,the one that occurs at the lowest dose. If individuals can be protected from this effect, whatever it mightbe, they will logically be protected from all other effects. Of course, this approach presumes that themost sensitive effect has been identified and dose–response relationship information for this effectexists. Obviously, for this to be effective, the toxicology of each chemical of interest must be reasonablywell characterized.In defining the risk problem, populations potentially at risk must be identified. These populationswould be groups of individuals with distinct differences in exposure, sensitivity to toxicity, or both.