THIS IS THE fourth and final MichiganScience article on risk assessment. These articles have been designed to acquaint and provide the reader with information that will allow him or her to understand and evaluate potential risks to human health resulting from exposure to chemicals, including drugs. In other words, this series on risk assessment was not designed to present the reader with an in-depth treatise on the complexities of risk assessment, but rather to provide a high level overview of the process. The hope was that enough information would be presented so that the reader, when faced with having to understand and make decisions relative to risk, would have the basic tools necessary to make an informed decision.

In the first three articles, we discussed the four basic steps in a risk assessment:

  • Hazard Identification
  • Dose-Response Relationships
  • Exposure Assessment
  • Risk Characterization

In the last article, we provided examples of a risk characterization for both a threshold chemical and a nonthreshold chemical (i.e. carcinogen) and discussed the uncertainties in the whole process. An expanded view of the risk assessment process would include a provision for additional data to enhance the overall process or to reduce the uncertainties in the final risk assessment number (see Figure 1). Also shown in Figure 1 is risk management, which is the focus of this article. The entirety of the process outlined in Figure 1 is in essence the process of risk analysis.

Figure 1: Risk Analysis

Figure 1: Risk Analysis - click to enlarge

A risk assessment simply cannot draw a distinct line between safe and unsafe. Safety is by its nature an inverse relationship of hazard. If the concept of safety is meant to simply mean the absence of risk resulting from exposure to chemicals, then this is nearly impossible to prove, because to do so requires proof that risk does not exist. Please recall from the earlier articles that it was pointed out that everything has a hazard or is toxic. It is best summed up, to paraphrase Paracelsus, as, "The dose makes the poison."

We can divide chemicals into three broad categories:

  • The enormous number of naturally occurring chemicals that reach us primarily through food.
  • Industrial chemical products that are produced for specific purposes.
  • Industrial pollutants - chemical byproducts of fuel use, of the chemical industry and of most other types of manufacturing (Rodericks).

If the goal is to be absolutely safe, or without risk, from these products, especially industrial chemicals or the polluting byproducts, then a wholesale banning would be necessary. This would require turning the calendar back 200 years or more (Rodericks). Therefore, the process of risk assessment is necessary to understand scientifically what the risk is from exposure from these sources and what is an acceptable level of exposure that would be without appreciable risk.

Once the scientific process is complete and the risks and uncertainties identified, decisions need to be made on how to manage the risk. This is perhaps the thorniest step in the overall process in the risk assessment paradigm. The risk assessor or those charged with protecting public health must make management decisions based on an evaluation of public health, economic, social and political consequences of a regulatory action. They must weigh competing priorities of individual freedoms, groups of individuals (i.e. the population as a whole), environmental groups, industry, etc. That is to say, judgments of acceptability of risky activities are not just a matter of numbers but draw on judicial, regulatory and political mechanisms through which societal choices are made and enforced. Some fundamental factors that must be considered in the management process are voluntariness, equity, procedural legitimacy, treatment of uncertainty and perceptions.

Voluntary vs. involuntary exposure is one key determinant in assessing risk acceptability. In a society that values individual liberties, the risk an individual is willing to take may be higher than a quantitatively similar risk that is imposed on an individual by another party. As a classic example, an individual can smoke cigarettes in the privacy of his or her home, creating a health risk for him or herself, and yet be forbidden to smoke in public, where this individual would impose a much smaller risk (via secondhand smoke inhalation) on others.

A second consideration in the management of risk concerns the fairness and equity of the distribution of risks and benefits. The concept of equity of risk is complicated by the fact that a risk management analysis that appears to be fair and equitable may turn out to be inequitable (though not perhaps unfair). This is very akin to the famous utilitarian dictum: "The needs of the many outweigh the needs of one."

Legal acceptability of risk is based on the answer to a fundamental question posed by society, regulators and industry, which is: How can disputes over risk be adjudicated and policy decisions made in the absence of adequate scientific information and knowledge about causal mechanisms? A critical issue, therefore, is "proof" in cases where it is not clear whether a risk is being imposed or where the magnitude of the suspected risk created by an exposure is highly uncertain. This will be discussed further below.

Uncertainties in the risk assessment process have been discussed in previous articles in this series. Uncertainty in the risk assessment process simply cannot be eliminated, and risk assessment and risk management cannot be clearly separated for uncertain risks. The decision of when to stop collecting data and to act is a risk management problem (Figure 1), while expressing the uncertainty at the time of transition from research to management is part of the risk assessment process.

Individual perception of risk cannot be ignored, but often these perceptions regarding risk are changeable, unreliable and overly sensitive to impressions. Many times, an individual's perception of risk is influenced by special interest groups that have an agenda and can make broad statements that may be true on the surface but are devoid of the fundamental concepts of dose and response. In other words, they may neglect to state that while a material is hazardous, the level at which exposure takes place may be in the range at which no appreciable risk occurs (i.e., exposure is devoid of risk or is at a level to which an individual may be exposed for some duration of time without an impact on health). Therefore, a risk may be perceived as large when in reality the risk to human health is negligible.

So how does one approach the task of risk management? There is a great propensity on the part of regulatory agencies and those who practice public policy to require numerical standards for judging what risks are acceptable. For non-cancer-causing chemicals, numerical thresholds are of great value. They reduce ambiguity and debate for the most part. The reason for this is that it is far easier to compare numbers than to evaluate the complexity of social decision processes.

One common approach to the risk management decision process is to conduct a cost-risk-benefit analysis when chronic health risks of an activity are known (Rodericks). The common practice in this approach is to evaluate risk control measures in the terms of dollars spent per statistical life saved. Balancing the costs against the benefits of risk control measures is clearly necessary for an efficient allocation of resources. To implement fully the cost-risk-benefit analysis approach, it is essential to develop more realistic measurements of the benefits from risk reduction than the conventional one of expected number of statistical lives saved. When risks are uncertain, a different set of issues must be confronted that essentially centers on the high costs of risk research, costs of risk control and uncertain benefits of possible risk reductions resulting from control measures.

It should be clear from the above discussion that one of the most challenging areas in statutory interpretation of risk assessment and risk management is the problem of setting cutoff levels or acceptable levels of exposure for risk regulators. The consistency and effectiveness of risk management decision-making might be enhanced if agencies had a systematic approach for determining whether specific risks are "de minimis" — that is, too trivial to warrant an expenditure of resources to assess or control them.[1]

Determining a de minimis risk level is essentially a pragmatic decision tool for distinguishing between trivial and nontrivial risks. In general, the de minimis approach is accomplished by establishing a risk cutoff level greater than zero. If a hazard is greater than the de minimis level, it becomes the object of possible regulation, up to and including a ban on the use of the chemical. If, however, the level falls below the de minimis level, it is excluded from further consideration. Ideally, a de minimis risk level would distinguish between small risks that are more costly to regulate than to tolerate and large risks that are more costly to tolerate than to regulate.

The de minimis approach is certainly consistent with current health and safety statutes and with regulatory agency efforts to establish insignificant risk levels in the evaluation of suspected hazardous chemicals. The fact that they are labeled insignificant risk levels rather than de minimis levels is not important. The logic underlying both is the same. For an example of this approach, let's refer back to the third article in this series, in which we evaluated chemical X and discovered that it had a reproductive effect with a NOEL or BMDL of 100 mg/kg/day. We applied a 100-fold uncertainty factor to the NOEL or BMDL and established an RfD of 1 mg/kg/day. The RfD established for this reproductive effect could, in essence, be considered the de minimis level below which there is an insignificant risk of a reproductive effect in women if exposed below this level for a lifetime.

On the other hand, how would we handle a nonthreshold chemical (i.e., a carcinogen)? Some argue, as stated in previous articles in this series, that there is no safe level of exposure to a carcinogen (i.e., the no-threshold hypothesis). What is true is that under the no-threshold hypothesis any exposure to a carcinogen increases the probability of cancer occurring, but it does not mean that any exposure to a carcinogen will cause cancer. Short of banning all carcinogens, if the above were true, regulators take the position that the "safe level" for exposure to a carcinogen is defined as the dose or exposure that produces no more than a specified and very low level of excess lifetime risk — generally 1/1,000,000, or one excess cancer in 1 million people exposed, which is sometimes expressed as 10-6. What does this mean? If we assume there are 300 million people in the United States, for example, exposed daily for their full lifetime to a concentration of a carcinogen that caused risk, then the number of extra cancer cases created over a 70-year lifespan would be (300 million people) x (1/1,000,000 extra lifetime risk per person) = 300 extra cancer cases during a lifetime, or an average of 300 ÷ 70 = four to five extra cases per year for an average lifespan of 70 years. Since the actual number of cases associated with 10-6 risk is probably lower than but certainly not more than the four to five extra cases per year, it would appear that a 10-6 risk level is an appropriate definition of protective of human health and that exposure below a level of one in a 1 million extra lifetime risk could be the de minimis level.

The Precautionary Principle

While the above approach seems reasonable to manage risk even with the uncertainties that are ever-present in the risk assessment process, there is a significant movement to manage risks in a much different approach, which is the use of the "precautionary principle." The precautionary principle, as it relates to environmental hazards, was proposed in January of 1998 at the Wingspread Conference held at the headquarters of the Johnson Foundation in Racine, Wis. At the conclusion of the three-day conference, a diverse group of scientists, philosophers, lawyers and environmental activists issued a statement calling for governments, corporations and scientists to adopt the precautionary principle:

"When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically. In this context the proponent [e.g. chemical manufacturer] of an activity, rather than the public, should bear the burden of proof [of a lack of harm]."

The precautionary principle is an extrapolation of the motto "better safe than sorry." While there is precaution involved in traditional risk assessment (note the 100-fold uncertainty factor used in the first de minimis risk calculation above), the precautionary principle is meant to address situations with higher degrees of scientific uncertainty about how and whether particular harms might be caused. The principle is intended for cases concerning potentially irreparable harm, such as birth defects or species loss.

Because the precautionary principle is applied in instances where scientific evidence and causality are not "fully established," critics observe that the principle may be invoked based on less-than-plausible risks and used to ban, rather than reduce exposure to, a process or product. The European Commission, which implements legislation passed by the European Union, "stresses that the precautionary principle may only be invoked in the event of a potential risk and that it can never justify arbitrary decisions. Hence, the precautionary principle may only be invoked when the three preliminary conditions are met — identification of potentially adverse effects, evaluation of the scientific data available and the extent of scientific uncertainty" (European Commission Communication).

In summary, this four-part MichiganScience series on risk assessment has attempted to provide the reader with a high level overview of the process of assessing risk to human health and the environment resulting from chemical exposures. It has tried to convey the complexities of the process and the uncertainties associated with this process, as well as to provide some insights into the most complex part of the process: risk management. This is by no means the complete picture. After these processes are complete comes the task of trying to communicate the risk to the general public, so they can understand and accept the safe exposure levels that are set.

[1] The term "de minimis" is derived from the Latin maxim "De minimis non curat lex," which means, "The law does not concern itself with trifles."

References and Further Reading

Rodericks, J.V., "Calculated Risks: The toxicity of human health risks of chemicals in our environment," Cambridge University Press, New York, N.Y., 1994.

National Academy Press, "Science and judgment in risk assessment," National Academy Press, Washington, D.C., 1994.

Paustenbach, D.J. (ed), "The risk assessment of environmental and human health hazards: A textbook of case studies," John Wiley and Sons, New York, N.Y., 1989.

"Europa: Summaries of EU Legislation: The precautionary principle," European Union, consumers/consumer_safety/l32042_en.htm (accessed May 16, 2010).