National Academy of Sciences. Biosolids Applied to Land:
Advancing Standards and Practices

Chapter 7: Integration of Chemical and Pathogen Risk Assessment [abridged]

The final element of the charge to the committee is to explore whether approaches for conducting pathogen risk assessment can be integrated with those for chemical risk assessment. This inquiry leads to a summary and synthesis of many of the previous chapters' findings and recommendations that resulted directly or indirectly from the committee's need to address the inherent uncertainty of the complex composition of biosolids. This uncertainty precludes the possibility of completely separating the risk-assessment and risk-management processes. Risk assessment for such mixtures is an ongoing process that requires quality control of treatment processes and some form of surveillance for adverse effects from exposure to biosolids. In this chapter, the question of whether pathogen risk assessment can be integrated with chemical risk assessment will be explored first in the agent-by-agent context of the original risk assessment used for the Part 503 rule and then in the broader and more recent context of risk assessment for complex mixtures.

AGENT-BY-AGENT RISK ASSESSMENT

The pathogen and chemical regulations of the Part 503 rule were developed differently. EPA conducted risk assessments for chemicals to establish concentration limits and loading rates but deemed microbial risk assessment to be too immature for developing risk-based limits for pathogens. Instead, EPA established treatment and site restrictions to reduce the concentrations of pathogens in biosolids. Advances in microbial risk assessment have occurred since then, but there remains a difference in the maturity of risk-assessment procedures for chemicals and those for pathogens. The question posed is whether this difference is simply an artifact of the different stages of development of these two branches of risk assessment or whether generic differences are attributable to the nature of the agents themselves. In addressing this question, it is useful to consider the four components of the traditional risk-assessment process (hazard identification, dose-response characterization, exposure assessment, and risk characterization) and ask which, if any, of those components has inherent differences in the way pathogens and chemicals are assessed.

Hazard identification is the process of reviewing relevant biological and chemical information on an agent that might pose a health hazard. Although there are obvious differences in the types of information available on chemicals and pathogens, there appears to be little fundamental difference in the process of identifying their hazards. This is supported by a recent NRC report Classifying Drinking Water Contaminants for Regulatory Consideration (NRC 2001), in which no distinction between chemical and biological contaminants is made. In general, however, pathogens usually are grouped into generic classes with less of an agent-specific focus than is common in chemical risk assessment.

The process for characterizing dose-response relationships is not as straightforward for pathogens as it is for chemicals. The process is complicated by the possibility that exposure to a pathogen may engender an immune response that might persist and alter an individual's subsequent susceptibility to infection or clinical disease. Acquired immunity has no relevant analog for chemical exposures in the risk-assessment context, although there are chemicals for which sustained exposure can result in tolerance for some toxic end points. Also, the converse can be true when an individual becomes sensitized to a chemical and develops serious and persistent hypersensitivity. For infectious agents, however, acquired immunity can be a major modifier of population risk. An exposed population is likely to be an unknown mixture of those with acquired immunity and those without. Moreover, the population can change over time as susceptible individuals become infected and move from one subgroup to the other. Acquired immunity might simply be addressed by developing two dose-response functions in the risk-assessment process, one for the susceptible population without immunity and a second for the population with acquired immunity. The conservative approach would be to conduct an assessment of a totally susceptible population, and although the results could be very conservative, this option would be consistent with EPA's practice of protecting sensitive subpopulations.

Perhaps the greatest methodological difference in the risk-assessment process for chemicals and pathogens occurs in the exposure assessment process. The difference is because of the possibility of secondary transmission of infectious agents (discussed in-depth below). The challenge posed by secondary transmission is that an individual is at risk not only from direct exposure to pathogens in biosolids but also from population-level interactions that can result in exposure to and infection from individuals already infected. In addition, there are environmental pathways (e.g., contamination of surface waters used for drinking or recreation) by which an individual infected with an enteric pathogen, for example, can alter the risk for populations not primarily exposed to the pathogen in biosolids. Whatever the pathway, secondary transmission can expand the population at risk beyond those involved in the original exposure scenario. Hence, the likelihood of secondary transmission is an issue that must be addressed generally in pathogen risk assessments, as contrasted with those for chemical exposures.

The risk-characterization process for a single pathogen versus a single chemical will differ in the need to account for the implications of acquired immunity and secondary transmission. In the case of biosolids, however, that distinction is somewhat academic, because both chemicals and pathogens are part of a complex mixture, the exact composition of which can change from time to time and place to place. As noted above and in Chapters 4 and 6, methods for conducting chemical and microbial risk assessments have advanced since the promulgation of the Part 503 rule, including methods for assessing risks of chemical mixtures. These advances are clearly relevant to updating the biosolids standards. However, the additional complexity of dealing with chemical and pathogen mixtures has the potential of being counter to the recommendations of the Presidential/Congressional Commission on Risk Assessment and Risk Management (1997). In particular, the commission advised a diminished reliance on assumption-laden procedures for arriving at agent-by-agent and medium-by-medium mathematical estimates of risk. Instead, it advises assessments focused at particular exposures and health end points, clarified with stakeholder input, with the objective of achieving and sustaining practical reductions in risk. Issues about mixtures are discussed further below, and the committee outlines data needs and the nature of studies that would inform more focused assessments in Chapters 2 and 3.

SECONDARY TRANSMISSION

Most quantitative risk assessments for pathogens have focused on ingestion of waterborne pathogens (Fuhs 1975; Haas 1983; Regli et al. 1991; Anderson et al. 1998). In these studies, static models were used to calculate the probability of individual infection or disease as a result of a single exposure event. This approach is based on an early chemical model for risk assessment (NRC 1983). In chemical risk assessment, there is generally a straightforward relation between risk to an individual and risk to a population of similarly exposed people. For example, if a particular exposure scenario results in an estimate of an individual risk of chemically induced disease of 1×10?4, then the expected number of cases in an exposed population of 100,000 is 10. This result is valid under the assumption that any person's probability of disease is independent of whether anyone else gets the disease. Both estimates of individual and population risk are determined by the dose-response function and the exposure assumptions, and both of those are unmodified by the disease status of others in the population. As noted above, that straightforward relation is not the case for all infectious diseases. For example, for an individual, the probability of infection from a particular pathogen in biosolids, PI, is the sum of two terms:

PI=P(directexposuretopathogen inbiosolids)+P(exposure topathogen shedby infected person)

The possibility of exposure to a pathogen shed by an infected person is peculiar to pathogens in being an important and sometimes dominant pathway of exposure. The pathway by which the shed pathogen gets from the infected to the susceptible person can be from direct contact or by circuitous routes through the environment.

The limitations of treating infectious disease transmission as a static disease process, with no interaction between those infected or diseased and those at risk, has been illustrated in studies of Giardia (Eisenberg et al. 1996), dengue (Koopman and Longini 1994), and sexually transmitted diseases (Koopman et al. 1991). However, risk-assessment approaches for environmentally mediated pathogen exposures involving secondary transmission are only now being developed (Colford et al. 2001). These approaches allow exploration of the importance of the secondary infection process. However, the need for data for execution of calculations based on these approaches is also greater than that for static risk assessments. When secondary infection is possible, risk is by definition manifested at a population level and risk calculations are dynamic in nature. (The overall risk calculation is based not only on current exposures to contaminated media but also on all subsequent secondary infections.) In addition, the existence and development of acquired immunity in the population must be accounted for in the analysis.

The dynamic systems approach was used to study the conditions under which environmentally mediated secondary transmission could be important in the transmission of Giardia (Eisenberg et al. 1996). An exposure scenario was studied in which swimmers were exposed to Giardia from a recreational swimming impoundment filled with water reclaimed from community sewage. The important finding in this study was that the rate of infected swimmers shedding pathogens into the impoundment was a crucial factor in determining (1) the degree to which a contribution of the incidence of giardiasis came from transmission via swimming; and (2) the most effective control strategy.

Clearly, the methods of risk assessment for chemicals and pathogens have inherent differences in some elements of the risk-assessment process. Thus, the committee concludes that in conducting single-agent risk assessments, there are inherent differences between chemical and pathogenic agents that must be considered. In particular, infection of an individual from exposure to pathogens in biosolids may lead to secondary infections in others from person-to-person contact or from transmission of the pathogen to others through air, food, or water.

The importance of secondary transmission depends in part on the level of acquired immunity to the pathogen in the community. In assessing the likelihood of secondary transmission, it is clear that the use of the dynamic modeling approach to fully assess the risks of the pathogen component of biosolids for all pathogens and all exposure scenarios would be a complex undertaking. Generally, site-specific data (e.g., population size) are required, and the models are themselves analytically complex. The use of default parameter values and appropriately structured analysis may be able to provide a practical procedure for using the modeling approach to explore the importance of immunity and secondary transmission in preliminary analyses. At present, however, it may be more practical to use less comprehensive methods as a form of preliminary analysis to address the importance of these effects. The objective of such a preliminary analysis would be to determine whether a particular pathogen possesses characteristics that result in secondary transmission and, if so, determine the possible pathways through which this transmission can occur.

For pathogens that can be transmitted via infected individuals, the preliminary analysis can proceed following the standard format of chemical risk assessment with the focus on the susceptible individual. A new feature of this process is the need to determine the existence of exposure pathways connecting a susceptible individual to others in the community assumed to be infected already. If plausible pathways do not exist, then no further analysis is needed. Alternatively, if such pathways are identified, it will be necessary to explore their importance. If their importance is low with respect to direct exposure, no further action is needed, whereas a significant risk with respect to background incidence of disease suggests the need for a comprehensive assessment.

From another perspective, the issue here is to gain some insight into what is termed the "force of infection" by infectious disease epidemiologists (Anderson and May 1991). The force of infection represents the probability that a given susceptible host becomes infected per unit time only because of the presence of other infected individuals in the population. A complicating feature of the concept is that the force of infection is generally assumed to be linearly proportional to the number of infected individuals in the population. This proportion in turn depends on the level of population immunity. Those factors again underscore that if pathways of secondary infection exist, it is only possible in an approximate way to carry out the preliminary analyses on an individual basis rather than at the population level. A feasible approach might be to conduct a two-tiered evaluation, the first dealing with the potential for secondary transmission of a set of candidate pathogens and the second analyzing the exposure pathways for those pathogens with a secondary transmission potential.

NOTE: THE BULK OF CHAPTER 7's MATERIAL IS NOT INCLUDED, JUST THE FOLLOWING FINDINGS AND RECOMMENDATIONS

FINDINGS AND RECOMMENDATIONS

Finding: Ideally, risk assessment of biosolids should be based on complex-mixture data to include risks from chemicals and pathogens. However, that type of data is not available in either sufficient quantity or quality (see Chapter 3), and methods have not been developed for integrating and characterizing the range of risks that might occur from exposure to mixtures of chemicals and pathogens. Thus, it remains necessary to use a component-based approach to assess risks from pathogens and chemicals in biosolids. The committee found that although the chemical-specific risk assessments conducted to establish the Part 503 regulations can be improved by using new risk-assessment methodology, the remaining uncertainty for complex mixtures of chemical and biological agents is sufficient to preclude the development of risk-management procedures that can reliably result in acceptable levels of risk. Some form of treatment-process quality assurance and ongoing surveillance must be done to ensure that effects not anticipated by the agent-specific risk assessments do not occur.

Recommendations:

Figure 7–1 should be used by EPA as a framework for managing the risks from exposure to biosolids. The framework includes audits of treatment-process performance and management practices, periodic hazard surveillance, and studies of health outcomes, including preplanned studies and studies in response to episodic events. For example, as recommended in Chapters 2 and 6, surveys should be conducted to verify that Class A and Class B treatment processes perform as assumed by engineering principles, and determinations of pathogen density and destruction across the treatment process and in the soil over time should be completed. Recommendations contained in Chapter 5 also address the need for process-performance measures that can be monitored and used in site-specific surveys of performance. In Chapter 3, the nature and objectives of hazard surveillance studies and studies of health outcomes of exposed populations are described more fully. All the recommendations reflect the committee's concern that the complex risk-assessment task posed by biosolids cannot serve as a useful and reliable guide without an ongoing effort to ensure that the assumptions underlying the assessment are valid and that the risk-management procedures put in place in response to the assessment are being routinely implemented. Broad-scale and site-specific feedback, graphically depicted in Figure 7–1, is needed.

Research should be conducted to synthesize existing information on potential interaction of chemicals and pathogens that might be associated with biosolids exposures and lead to an increased susceptibility to infection, particularly by inhalation.

Finding: Methods for conducting chemical and microbial risk assessment have advanced since the promulgation of the Part 503 rule in 1993. In reviewing these methods, the committee found that there are inherent differences between chemical and pathogenic agents that must be considered in single-agent risk assessments. In particular, infection of an individual from exposure to pathogens in biosolids might result in secondary infections in others. The secondary infections might be caused by person-to-person contact or transmission of the pathogen to others through air, food, or water. The importance of secondary transmission depends in part on the level of acquired immunity to the pathogen in the community. Another development of importance is the recommendation of the Presidential/Congressional Commission on Risk Assessment and Risk Management to diminish reliance on assumption-laden procedures for arriving at agent-by-agent and medium-by-medium mathematical estimates of risk in favor of stronger interaction with stakeholders in achieving and sustaining practical reductions in risk.

Recommendation: As outlined in Chapters 5 and 6, future risk assessments of biosolids components should be conducted using the most current methods and data. For pathogens, it is important that risk assessments include an evaluation of the potential for secondary transmission of disease. Representatives from all stakeholders should be included in future risk assessments. Stakeholders can provide information and insights into the use of biosolids in practice and the potential health problems, which are particularly important in the development of exposure assessment. Involving stakeholders throughout the risk-assessment process provides opportunities to bridge gaps in understanding language, values, and perspectives.

Finding: The committee is aware that this report poses a challenge to EPA in that much of the discussion in this chapter, as well as in Chapters 3 and 4, recommends very different emphases in updating the Part 503 rule than are reflected in the charge to the committee. In many ways, the contents of Chapters 2, 5, and 6 are a more direct response to the charge, which is grounded in the original approach and methodology, while acknowledging that this review would be carried out in the context of new developments. However, the committee believes that the differences in point of view and approach underlying its response to the various elements of the charge accurately reflect the counter-vailing currents in the broader risk-assessment community and the differences in perspective among those directly involved in the management of biosolids risks. The overall objective of the process, which this report is a part of, is to better assess and manage the risks associated with the land application of biosolids in the United States.

No recommendation: