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3 Review of Key Concepts, Assumptions, and Decisions Made in Developing TG-248, TG-230, and RD-230 This chapter provides an overview of some of the general concepts discussed and key assumptions and decisions made by the U.S. Army Cen- ter for Health Promotion and Preventive Medicine (USACHPPM) in devel- oping Technical Guide 248 (TG-248), Technical Guide 230 (TG-230), and Reference Document 230 (RD-230), emphasizing the issues identified in the subcommitteeâs statement of task. The subcommittee evaluated the follow- ing aspects of the Armyâs guidance: the use and adaptation of pre-existing exposure guidelines for deployment purposes; population susceptibilities; exposure factors; acceptable lifetime cancer risk; immediate and long-term health effects; aggregate exposure and cumulative risk; exposure assess- ment; and the utility of the guidance for decision makers. USE OF PRE-EXISTING EXPOSURE GUIDELINES Military exposure guidelines (MEGs) were developed by USACHPPM for contaminants in air, water, and soil. They were derived by reviewing the guidelines of other agencies (e.g., the U.S. Environmental Protection Agency [EPA], the Occupational Safety and Health Administration [OSHA]), selecting the most relevant guidelines on the basis of a hierarchi- cal scheme, and modifying the chosen guidelines for military use. The 47
48 TECHNICAL GUIDES ON ASSESSING AND MANAGING CHEMICAL HAZARDS drawback of this approach is that the existing guidelines were designed to protect different populations (e.g., the general population, workers) and were intended for different settings (e.g., ambient exposures, workplace, accidental releases), which made it necessary for USACHPPM to adjust the values to make them relevant to the military population in the deployment setting. Problems with using pre-existing guidelines and adjusting them for deployment purposes are described below. Procedures for Developing Noncancer and Cancer Health Assessments The following procedures typically are used by regulatory and other agencies to establish health-protective exposure guidelines and therefore form bases of the MEGs. Noncancer Assessments Most noncancer assessments begin by selecting a no-observed-adverse- effect level (NOAEL) from experimental data and adjusting and extrapolat- ing that value by applying factors to account for uncertainties related to exposure duration, varying levels of susceptibility among humans or be- tween species when animal data are being used, and other facets of the data. Typically, the adverse effect having the lowest NOAEL in the most sensi- tive species for which data are available is chosen as the critical toxicity end point for derivation of the guideline. The assumption is that if the popula- tion is protected from that adverse effect, it will also be protected from the other adverse effects observed at higher concentrations. NOAELs can be determined by identifying the lowest NOAEL from a single critical study or by doing a benchmark dose analysis and selecting the mathematical result to use as a surrogate NOAEL. Data from the selected study or studies of interest are typically transformed to a product of concentration and time (i.e., C Ã t) to account for differences between the exposure duration used in the study or studies and the duration for which the health-protective guideline is being established. The NOAEL is adjusted by the use of uncertainty factors (UFs). These factors are applied to account for uncertainties in extrapolating experimental animal data to humans (interspecies differences) or variable susceptibilities in the human population (intraspecies differences); to represent the expected ratio of the lowest-observed-adverse-effect level (LOAEL) to NOAEL
REVIEW OF KEY CONCEPTS, ASSUMPTIONS, AND DECISIONS 49 when a LOAEL is used instead of a NOAEL; to account for uncertainty in predicting chronic exposure effects on the basis of subchronic exposure studies; and to provide a margin of safety when the database is incomplete (sometimes referred to as a modifying factor). Standardized UFs are de- rived from literature comparisons (e.g., comparing results from a subchronic and chronic study to estimate what value might be applied to a subchronic result to conservatively predict the chronic result). UFs are not statistically derived indicators of uncertainty, and most are used to account for missing information (e.g., only subchronic data exist, but a chronic exposure value is needed). Thus, each application of a UF indicates that key information required to predict a chemical-specific toxic end point is not available; it must instead be addressed by using a default estimate of the potential mag- nitude of the corresponding impact of that factor on the likelihood of the end point of concern. The factor sometimes applied to account for intra- species differences is more appropriately referred to as a variability factor, insofar as it is applied to address interindividual heterogeneity and not uncertainty. Most UFs are either 10 (a log), 3 (half a log), or 1 (no UF). EPA uses all of the UFs described above, as needed, up to a maximum of 10,000 for reference doses (RfDs) and 3,000 for reference concentrations (RfCs). The maximum for the RfC is lower because interspecies differences are handled by using a combination of a dosimetric extrapolation and a maximum UF of 3 for pharmacodynamic differences. The minimal risk levels (MRLs) of the Agency for Toxic Substances and Disease Registry (ATSDR) include all of the UFs except the duration adjustment, because guidelines are devel- oped for several durations. The use of UFs differs among the existing exposure guidelines, leading the current MEGs to vary in their conservatism. Table 3-1 presents the UFs that underlie some of the MEGs. The table shows that some of the applied UFs are not relevant to the deployed population, as is the case for the UFs for phosphine. In other cases, it could not be determined whether UFs were used, which makes it impossible to assess the level of protection provided. USACHPPM attempted to make adjustments to account for the differences in characteristics between the deployed and general population, but the subcommittee found the adjustments were not sufficient to ensure that the resulting MEGs provide comparable levels of protection among chemicals. Chapter 5 provides a more detailed description of the procedures used by various organizations to derive their exposure guidelines, a summary of adjustments applied by the military, and recommendations for making improvements in the MEGs.
50 TABLE 3-1 Implied Underlying Basis of 1-Hour Air MEGs for Selected Chemicals 1-Hour Chemical Air-MEG Basis Species UH V UL UD Acrolein Significant AEGL-2 (P) Human 1 3 1 1 Severe AEGL-3 (P) Animal 3 3 1 1 Acrylonitrile Significant ERPG-2 Human NS NS NS NS Severe ERPG-3 Animal NS NS NS NS Arsine Significant AEGL-2 (F) Animal 10 3 1 1 Severe AEGL-3 (F) Animal 10 3 1 1 Bromine Significant AEGL-2 (P) Human 1 3 1 1 Severe AEGL-3 (P) Animal 3 3 1 1 Chlorine Significant AEGL-2 (I) Human 1 1 1 1 Severe AEGL-3 (I) Animal 3 3 1 1 Diborane Significant AEGL-2 (F) Animal 3 3 1 1 Severe AEGL-3 (F) Animal 3 3 1 1 Formaldehyde Significant ERPG-2 Human NS NS NS NS Severe ERPG-3 Animal/Human NS NS NS NS Hydrogen chloride Significant AEGL-2 (I) Animal 3 3 1 3a Severe AEGL-3 (I) Animal 3 3 1 1 Hydrogen cyanide Significant AEGL-2 (F) Animal 2 3 1 1 Severe AEGL-3 (F) Animal 2 3 1 1 Hydrogen fluoride Significant AEGL-2 (I) Animal 3 3 1 1
Severe AEGL-3 (I) Animal 1 3 1 2b Hydrogen sulfide Significant AEGL-2 (I) Animal 3 3 1 1 Severe AEGL-3 (I) Animal 3 3 1 1 Nitric acid Significant AEGL-2 (R) Human 1 3 1 1 Severe AEGL-3 (R) Animal 1 3 1 1 Phosgene Significant AEGL-2 (F) Animal 3 3 1 1 Severe AEGL-3 (F) Animal 3 3 1 1 c Phosphine Significant AEGL-2 (R) Animal 3 10 1 1 Severe AEGL-3 (R) Animal 3 10c 1 1 Sulfuric acid Significant ERPG-2 Animal/Human NS NS NS NS Severe ERPG-3 Animal/Human NS NS NS NS a Sparse data. b The highest nonlethal value was close to the LC50 (concentration lethal to 50% of subjects) value. c Children appear to be more susceptible. Abbreviations: F, final value published by NRC (2000a, 2002, 2003); I, interim value under review by NRC; NS, not specified; P, proposed but not yet published in the Federal Register for public comment; R, interim value published in the Federal Register for public comment; UH, factor that reflects uncertainty associated with interspecies variability (i.e., animal-to-human toxicity extrapolation); UL, factor that reflects uncertainty associated with LOAEL-to-NOAEL extrapolation; UD, modifying factor that reflects uncertainty associated with incomplete data; V, factor that reflects intraspecies variability in susceptibility to specified toxicity. Sources: AIHA 1988, 1989, 1997; EPA 2002a,b,c,d,e,f, 2003a,b; NRC 2000a, 2002, 2003. 51
52 TECHNICAL GUIDES ON ASSESSING AND MANAGING CHEMICAL HAZARDS Cancer Assessments Cancer assessment methods are currently in transition, so the methods used to assess cancer in TG-230 can only be understood by reviewing the underlying documentation. Generally, the cancer-risk values used by USA- CHPPM are based on older methodology that assumes that carcinogens have nonthreshold mechanisms and modes of action. Using that methodol- ogy, exposures to carcinogenic chemicals at any level are assumed to in- crease the risk of cancer development. Chemicals are classified into catego- ries based on their likelihood of being carcinogenic to humans. For exam- ple, EPA (51 Fed. Reg. 33992 ) used the following classifications: â¢ A. Known human carcinogen, based on adequate human data. â¢ B1. Probable human carcinogen, based on limited human evidence. â¢ B2. Probable human carcinogen, based on data from animals and inadequate or no evidence in humans. â¢ C. Possible human carcinogen. â¢ D. Not classifiable. Newer methodologies (EPA 1999) use information on the modes and mechanisms of action of a chemical to assess risk, and a nonthreshold as- sumption is used only as a default when the mechanism of action is un- known. Agencies such as EPA evaluate the weight-of-evidence to estimate the degree to which each chemical might be a human carcinogen, and the assessment is described rather than categorized. The typical quantitative cancer assessment underlying the Armyâs MEGs relies on linear extrapolation of the data from the concentrations in the study being used to zero. A âslope factorâ is generated that is the upper bound (usually the 95% confidence limit) of the increased cancer risk from a lifetime exposure. Typically, that factor is expressed either as increased risk per unit dose (e.g., in units of risk per milligram per kilogram per day [(mg/kg/day)-1]) or as increased risk per microgram per liter of drinking water ([:g/L]-1) or microgram per cubic meter of air ([:g/m3]-1). The slope factor is expressed as the upper bound of risk. Thus, the risk is unlikely to exceed the upper bound value and is likely to lie somewhere between zero and the upper bound. UFs are not applied in the traditional cancer assessment procedures. Newer methods that are more mechanism-based have options for consider- ing linear and nonlinear extrapolations and the use of UFs. TG-230 and RD-230 should be updated to reflect the most recent approaches to cancer
REVIEW OF KEY CONCEPTS, ASSUMPTIONS, AND DECISIONS 53 assessment, with the understanding that most of the existing cancer guide- lines set by other agencies are not based on the newer methodologies. Population Susceptibilities Assumptions about sensitivity and susceptibility are incorporated into the development of health-related guidelines. Within an exposed popula- tion, exposures are rarely identical, and even when exposures are equal, doses to target tissues and cells are not the same in all people. People ex- posed to similar doses do not always have similar health outcomes. Protect- ing individuals or subpopulations that are more susceptible to adverse ef- fects is a goal of most, if not all, health guidelines. The key question for deployed forces is who among the military population is likely to be more susceptible? Susceptible groups include those who might exhibit a greater effect in response to particular exposures. Some factors that might make individuals more susceptible include age, health status, and genetics. His- torically, it has been assumed that the healthy men and women volunteers composing the military population would have few predisposing conditions that might make them sensitive or susceptible to environmental chemicals. In contrast, TG-230 and RD-230 assume that deployed populations include a more substantial representation of subpopulations that might be more sensitive to chemical exposures. USACHPPMâs rationale for considering those subgroups in the development of MEGs is based almost entirely on a white paper by Weese provided in an appendix to RD-230. According to data provided by USACHPPM (unpublished data, 2002) on the demographic characteristics of Persian Gulf War participants, the population in the theater of operations was 93% male with a median age of 24 years. The force consisted of 83% active duty personnel, and Army personnel made up 50% of the total. The crucial question about the de- ployed military population is whether it is different from the general popu- lation for risk-assessment purposes. Obviously, the two populations are not identical, but are there enough sensitive individuals in the military popula- tion to justify protecting for the same susceptibilities exhibited in the gen- eral population? TG-230 and RD-230 treat the factors in the military popu- lation that predispose individuals to sensitivity to chemicals as similar to and of the same magnitude as factors in the general population, excluding some groups such as children and the elderly. Some of the factors that were evaluated with regard to the military include genetic variability, asthma, and the embryo or fetus, primarily during the first trimester when pregnancy might not yet be detected.
54 TECHNICAL GUIDES ON ASSESSING AND MANAGING CHEMICAL HAZARDS Genetic variability is a subject that has received renewed interest due to the mapping of the human genome and recent research into genetic poly- morphisms. Genetic variability is probably present in the military popula- tion at about the same level as it is in the general population. However, genetic variability does not comprise the whole of human variability in responses to chemicals, just as genetic make-up does not totally determine human responses in any other aspect of life. Variability in responses to chemicals results from differences in age, gender, nutritional status, and lifestyle factors in addition to genetic background (Calabrese and Gilbert 1993). Genetic variability that causes an individual to be sensitive to one type of chemical might not result in changes in sensitivity to other types of chemicals when the mechanisms of toxicity are different. The distribution of genetic variability might not reflect the ultimate variability in responses to a chemical, because additional compensatory mechanisms, such as redun- dant pathways, homeostatic mechanisms, and repair processes, could oper- ate. At present, there is insufficient information to explicitly incorporate genetic susceptibility into exposure guidance except in the case of a few chemicals, including chemical warfare agents that act through cholin- esterase inhibition. There are about 17 million asthmatic individuals in the United States (AAFA 2003), and they make up about 6% of the general population. When reliably diagnosed at any age, asthma, including reactive airway disease, exercise-induced bronchospasm, or asthmatic bronchitis, is cause for rejection in appointments, enlistments, and inductions into the U.S. Armed Forces (U.S. Department of the Army 2002). Furthermore, if the asthma diagnosis is in doubt, tests for reversible airflow obstruction or airway hyperactivity must be performed prior to acceptance into the mili- tary. Asthma is a cause for referral to a medical evaluation board for possi- ble separation from the service (U.S. Department of the Army 2002). Al- though complete physical examinations of service members are not con- ducted prior to deployment, medical records of possible deployment person- nel are screened for medical conditions that would preclude the service members from duty. In the cases of service members who develop asthma while on active duty, the condition should be documented on their medical records. A service member with asthma can be placed on a temporary medical profile for 1 year. At the end of that year, he or she must be able to meet all the requirements for duty and training, including the running standards of the physical training test. It is expected that the percent of asthmatic individuals in the general military population and, more specifi- cally, among deployed forces is much lower than that in the general popula-
REVIEW OF KEY CONCEPTS, ASSUMPTIONS, AND DECISIONS 55 tion. Also, any cases of asthma that might be encountered during a deploy- ment would be expected to be mild given the screening executed by the military. According to the white paper by Weese presented in RD-230, only 15% of service members are female, and less than 7% of the forces deployed during the Persian Gulf War were female. Female soldiers are not deployed if they are known to be pregnant; however, there is the possibility that some women might not know they are pregnant at the time of deployment or might become pregnant during deployment. First trimester embryos or fetuses are considered a sensitive subpopulation by USACHPPM, even though the potential number of them in the deployed population is probably very small. However, some MEGs do not appear to be protective in this regard. For example, the 2-week water MEG for dinoseb is 0.14 mg/L, which would yield an exposure approximately 30 times greater than EPAâs RfD of 0.001 mg/kg/day set for fetal protection (EPA 1989). Lead is also a special consideration (see Box 3-1). Most of the existing guidelines used by USACHPPM to determine MEGs were developed for target populations other than the military. That means that different population characteristics and susceptibility factors were used in developing those guidelines. See Table 3-2 for the names of guidelines set by other organizations and the populations they were meant to protect. Guidelines developed for the general public usually include factors to protect susceptible subpopulations that might be more sensitive because of their age (e.g., infants, children, and elderly) or health status (e.g., pre-existing disease). Guidelines such as EPAâs RfDs, RfCs, and acute exposure guideline levels (AEGLs) include UFs to calculate exposure values expected to be protective of those sensitive subpopulations. Other guidelines, such as the emergency response planning guidelines (ERPGs) and temporary emergency exposure limits (TEELs), are developed to pro- tect most individuals in the general public but not particularly sensitive individuals. For guidelines in the workplace, such as Threshold Limit Values (TLVs) and immediately dangerous to life and health (IDLH) val- ues, it is assumed that the worker population is composed of relatively healthy adults, and therefore, the standards are not designed to be protective of sensitive subpopulations. There are a few guidelines that have been developed specifically for the military population, including continuous exposure guidance levels (CEGLs) and field drinking water standards (FDWS). For those military standards, no special consideration was given to susceptible individuals. Table 3-3 shows the order of priority given to existing guidelines in establishing MEGs.
56 TECHNICAL GUIDES ON ASSESSING AND MANAGING CHEMICAL HAZARDS BOX 3-1 Evaluation of the Protectiveness of the 14-Day Water MEG for Lead The water MEG for lead was calculated using a criteria value of 50 micrograms per liter (:g/L) published by the World Health Organization (1996).a Bowers (2003) mod- eled lead in blood at the request of the subcommittee using the specific parameters em- ployed by USACHPPM. The model was derived from research by OâFlaherty (1993). The following exposure assumptions were made: a young woman born in 1980 ingested 15 L of water per day with lead at 50 :g/L for 2 weeks at the age of 23 and then returned to a normal water consumption rate of 2 L of water per day with lead at background concentrations. This results in a maximum blood lead concentration of 14 :g per deca- liter (dL) for the woman, and it would typically take a little more than 6 months to return to original baseline levels. The embryo or fetus is generally assumed to have a blood lead level 0.9 times that of the mother, so fetal blood lead would peak at 12.6 :g/dL and would stay above 10 :g/dL, EPAâs suggested maximum, for at least 2 weeks. The protectiveness of the MEG is ambiguous. In fetal development, a day or even a few hours can mean the difference in susceptibility to the developmental toxicity of an environmental agent as well as the qualitative and quantitative nature of the effects. For that reason, exposures to the developing organism might be acute but have chronic outcomes. Thus, the number of days of exposure to the pregnant animal might be irrele- vant. Therefore, an excursion of 26% over the accepted blood lead level might not be protective of the embryo or fetus, particularly in view of new findings that call into question the generally accepted âsafeâ level of 10 :g/dL (Canfield et al. 2003). _______________________ a The subcommittee subsequently discovered that WHOâs drinking water guideline was incorrectly reported by USACHPPM. The correct value is 10 :g/L. Using the same exposure scenario above, but a lead concentration 10 :g/L, the peak blood lead level was found to be 4 :g/L. The blood lead level would return to baseline somewhat faster than the time estimated above for a 50 :g/L exposure. A 4 :g/L exposure would not be expected to affect the embryo or fetus, using the presently defined âsafeâ blood lead concentration of 10 :g/dL. To consider susceptible subpopulations in the calculations for establish- ing noncancer exposure guidelines, a UF of 10 for human variability is typically applied (Haber et al. 2002). That factor is expected to cover dif- ferences in age, gender, genetics, and pre-existing disease that might make some individuals more susceptible to adverse effects from chemical expo- sures. Several sources have suggested that the UF of 10 should be divided into approximately equal pharmacokinetic and pharmacodynamic factors (Renwick and Lazarus 1998; Gentry et al. 2002). There is clear evidence of differences between the deployed military population and the general population that would tend to make the deployed military population less sensitive. For example, there are fewer asthmatic individuals (and presum- ably no severe asthmatic patients) in the deployed population than in the general population. The assumption that the military population is as susceptible to the health effects of hazardous chemicals as the general population would lead to excessively conservative estimates of acceptable exposures. For example,
TABLE 3-2 Target Populations for Existing Exposure Guidelines Used in the Development of MEGs Exposure Guideline Organization Target Population AEGLs (acute exposure guideline levels) U.S. Environmental Protection Agency General public, including sensitive subpopulations HAs (health advisories) U.S. Environmental Protection Agency General public, including sensitive subpopulations MRLs (minimal risk levels) Agency for Toxic Substances and Disease General public, including sensitive Registry subpopulations PMEGs (preliminary military air guidelines) U.S. Army General public, including sensitive subpopulations RfDs (reference doses) U.S. Environmental Protection Agency General public, including sensitive RfCs (reference concentrations) subpopulations SPEGLs (short-term public emergency National Research Council General public, including sensitive guidance levels) subpopulations ERPGs (emergency response planning American Industrial Hygiene Association General public guidelines) TEELs (temporary emergency exposure limits) Department of Energy General public IDLH (immediately dangerous to life and National Institute for Occupational Safety and Worker population health) Health TLVs (Threshold Limit Values) American Conference of Governmental Worker population Industrial Hygienists EEGLs (emergency exposure guidance levels) National Research Council Military personnel CEGLs (continuous exposure guidance levels) National Research Council Military personnel FDWS (field drinking water standards) U.S. Army Military personnel 57
58 TECHNICAL GUIDES ON ASSESSING AND MANAGING CHEMICAL HAZARDS TABLE 3-3 Existing Guidelines Listed in Order of Priority for Use in the Development of MEGs Short-Term Long-Term Air 1 hour 8 hours 14 days Water Air Water Soil AEGLsa AEGLsa CEGLs FDWS PMEGsa FDWS RfDsa ERPGs TLVs MRLsa HAa TLVs HAa a a TEELs TLVs MRLs MRLs MRLsa Other Special RfDsa Other a Protective of sensitive subpopulations. MEGs for carbon monoxide were based on EPAâs national ambient air quality standards (NAAQS), which were set to protect exercising angina patients. Angina patients would not be part of the deployed population, so that level of protection is not necessary for military personnel. A National Research Council (NRC 2000b) report makes the following important dis- tinctions between military and civilian risk assessment: Incorporating âmargins of safetyâ or conservative estimates of acceptable exposures, as is frequently done in environmental and occupational health settings, is not always useful to the needs of military risk management. When a high level of health and safety protection can be achieved without undue burdens or increases in other risks, such margins can be part of an effective risk-manage- ment program. But when risks must be borne or when probabilities of casualties must be weighed against immediate military consider- ations, best estimates of probable impact are more useful. When the guideline used for deriving a MEG was designed to protect sensitive subpopulations (see Table 3-2), an adjustment factor should be applied (i.e., multiplied to remove the intraspecies UF that was used in the original derivation). For example, if an AEGL includes a UF of 10 to ac- count for the susceptibilities of populations not likely to be deployed, that factor should be backed out of the guideline before it is used as the basis for a MEG. When the standard used to derive a MEG was designed to protect a military or healthy population (see Table 3-2), no UF should be applied to account for susceptible subpopulations unless there is a chemical- or population-specific reason to do so.
REVIEW OF KEY CONCEPTS, ASSUMPTIONS, AND DECISIONS 59 In determining MEGs, USACHPPM sometimes modified guidelines that incorporated an intraspecies UF by reducing the UF. For four short- term water MEGs (ammonium sulfamate, hexazinone, diisopropyl methylphosphonate, and isopropyl methylphosphonate) derived from EPAs health advisories (HAs), an adjustment was made to reduce the UF of 10 applied to protect for sensitive people in the general population. That was accomplished by multiplying the HAs by a factor of 3. USACHPPM con- sidered applying a factor of 10 to all of the EPAâs HAs, but decided to use the more conservative approach instead. The subcommittee is concerned that inconsistent adjustment of standards meant to protect the general popu- lation has resulted in inconsistently conservative MEGs (see Chapter 5 for discussion of media-specific MEGs for more details). The subcommittee believes that military decision making would be better served by MEGs chosen consistently and likely to protect nearly all exposed deployed military personnel from chemical toxicity, consistent with DOD Safety and Occupational Health Program Instruction 6055.1 (August 19, 1998), to the extent feasible in the context of mission deployment. MEGs should reflect any well-documented differences in susceptibility or sensitivity to chemical-specific injuries between the mili- tary population and the general U.S. worker population. Such differences might be expected if the U.S. military deployed population has a demon- strated lower incidence of sickness, asthma, or obesity, or an absence of children or women past month 2 of pregnancy compared with the U.S. worker population. Any MEGs for deployed military personnel that are less restrictive than corresponding occupational guidelines used for U.S. work- ers (including DOD personnel stationed in the U.S.) should clearly be justi- fied by reference to specific DOD-enforced operational conditions and/or to well-documented clinical-survey data. In contrast, the subcommittee acknowledges that military decision making would be best served by CCEGs that employ no UFs for intraspe- cies differences unless there is specific evidence that some members of the deployed population are likely to be more sensitive to a specific chemical and that evidence would not otherwise be reflected in dose-response infor- mation used as the basis for a CCEG. That is, a UF for intraspecies differ- ences should be applied to develop a CCEG only in cases where doing so improves the accuracy of that CCEG. For example, the accuracy of CCEGs would be improved in situations where the application of an intraspecies UF adjusts for bias introduced by using human data that inadequately reflect or do not reflect a sensitive subpopulation that reasonably can be anticipated to be present among deployed military personnel as the basis for dose-re- sponse estimation.
60 TECHNICAL GUIDES ON ASSESSING AND MANAGING CHEMICAL HAZARDS Exposure Factors When assessing chemical risks, it is necessary to make assumptions about the rate of exposure through various routes. In TG-230 and RD-230, USACHPPM assumes that deployed troops have higher activity levels than the general population, which increases their ventilation and water con- sumption rates and thereby increases exposures to contaminants by those routes. USACHPPM evaluated available data on soldier-specific activities and exposure data from the EPA Exposure Factors Handbook (1990) and calculated a higher daily inhalation rate of 29.2 cubic meters (m3) per day compared with EPAâs default value of 20 m3/day. Similarly, USACHPPM assumes that water consumption is much higher among deployed forces than the general public (which averages 2 liters [L] per day). Typically, the military assumes consumption of 5 L/day, but in dry, arid climates that rate could be as high as 15 L/day. These higher rates have been validated and established in Army doctrine (U.S. Department of the Army 1999) and are consistent with reports from the Israeli Defense Forces and U.S. Army Medical Services officers in the Mojave Desert (Henry 1985). The subcom- mittee supports the use of increased ventilation and water consumption rates for deployment risk assessments. It is important that these assumptions be consistently applied (see Chapter 5 for discussion of how the ventilation rate adjustment does not appear to have been applied to some of the 14-day MEGs). Other exposure adjustments were sometime applied to the pre-existing guidelines to make them relevant to the exposure duration of interest to USACHPPM. Those adjustments are detailed and evaluated in Chapter 5. ACCEPTABLE CANCER RISK The Army requested that the subcommittee review its selection of an acceptable cancer risk of 1 in 10,000 (1 Ã 10-4). The selection of an accept- able risk level is a policy decision, and the subcommittee does not believe it would be appropriate for it to make a judgment about how much risk the military should accept. However, the subcommittee decided that it could address this task by reviewing the acceptable risk levels selected by other organizations and making observations about where the Armyâs acceptable cancer risk threshold lies in comparison and the rationale used to set the threshold. With regard to chemical exposures, âsafetyâ is often defined by various terms that include both scientific components and components that reflect societal values. In those instances where risk of injury can be quanti-
REVIEW OF KEY CONCEPTS, ASSUMPTIONS, AND DECISIONS 61 fied, safety also is expressed as levels of risk at which the consequences are considered to be of little or no concern (de minimis or acceptable risk) or require intervention (de manifestis risk). The technical guides distinguish between chemical substances that can cause cancer and chemical substances that reportedly cannot. RD-230 indicates that health- or medical-risk acceptability applies solely to expo- sures to carcinogens, because noncarcinogens are governed by biological thresholds below which no injury is likely to occur. RD-230 further indi- cates that the acceptable risk of excess cancer resulting from exposures to chemical carcinogens is 1 Ã 10-4 regardless of route of exposure (e.g., inha- lation, ingestion). Because 1-year MEGs are established using this risk level, the issue that is addressed is the incremental cancer risk averaged over a lifetime from a 1-year deployment. The rationales in RD-230 for the selection of the acceptable risk value are (1) that it is the upper bound of the range of cancer risk found acceptable to EPA (1 Ã10-4 to 1 Ã 10-6) (EPA 2001a) and (2) that it is an order of magnitude less than the acceptable level of risk generally supported for workers by the Occupational Safety and Health Administration (Rodricks et al. 1987). The need to identify acceptable levels of risk rose to prominence in the debate over potential exposures to carcinogens present in the environment and in the workplace. On the basis of observations from radiation biology and theories of carcinogenesis, the concept that nonthreshold effects can result from exposures to carcinogens (or mutagens) was adopted for regula- tory purposes.1 The theory was that any exposure to a carcinogen carries with it some probability of an irreversible degree of damage, so no expo- sures to carcinogens can be judged risk-free, however small. In the past, pathological events thought to have a threshold were controlled by identify- ing the biological threshold, adjusting it by UFs, and keeping exposures below it (a âyes or noâ decision). With the advent of the nonthreshold approach representing a continuum of risk, and the impracticability of main- taining a zero-risk policy, the issue of how much added risk was acceptable had to be addressed. Identifying acceptable risk levels has been a subject of debate and dis- agreement for many years. For example, a Supreme Court decision regard- ing Section 112 of Clean Air Act cited a mandate that EPA identify âan acceptable level of riskâ for human exposure to carcinogens (without regard to cost or technical feasibility) and to employ an âample margin of safetyâ 1 The concept that biological thresholds do not exist for carcinogens is no longer current (EPA 1999; see discussion earlier in this chapter). USACHPPM should update its technical guides accordingly.
62 TECHNICAL GUIDES ON ASSESSING AND MANAGING CHEMICAL HAZARDS to protect the public health (Natural Resources Defense Council v. U.S. Environmental Protection Agency 824 F.2nd1146 )). In that case, however, the court was likely advocating, although indirectly, that a risk ceiling, above which inherently unsafe activities should be regulated with- out regard to cost, be used as the de manifestis acceptable risk level. The court suggested that an acceptable risk level could be determined by adopting a âreasonable person standard.â Risks associated with normal everyday activities (e.g., driving a car) and accepted by the general public could be considered acceptable (also referred to as ârevealed preferenceâ). Of course, that assumes that the true risks associated with activities are accurately known and understood by the participants in those activities. Given that the actual lifetime risk of a fatal car accident (2 Ã 10-2), generally accepted by the public, is much higher than the estimated risks apparently tolerated for environmental pollution (1 Ã 10-4 to 1 Ã 10-7) or occupational disease (1 Ã 10-3), other factors clearly influence the decision of how much risk to tolerate, and the level of acceptable risk might well vary according to circumstance. As noted by Whipple (1988), the existence of a large risk does not excuse a small one when the benefits and other contextual factors are different, but social concerns and attention to risk should bear some relation to the magnitude of the risk under consideration. At this juncture, cost and benefit enter the decision-making process. There are examples of high-risk activities that have correspondingly high benefits being tolerated (e.g., some medical treatments); of high-risk activities that have low bene- fits being rejected; and of low-risk activities that have low benefits being evaluated on a case-by-case basis with considerable subjectivity. Another means of selecting an acceptable risk level is to identify the risks associated with rare events that people face and presumably accept as consequences of everyday life (e.g., deaths from lightning strikes, torna- does, bee stings, shark attacks). Actuarial data suggests those risks fall in the range of 1 Ã 10-6 (Whipple 1988). Numerous scholarly works exist on the subject of acceptable risk (Lowrance 1976; Fischhoff et al. 1981; Whipple 1988). Most confine themselves to identifying the proper characteristics of the decision-making process for acceptable risk and the difficulties associated with that effort. Some of the issues used to judge acceptability include whether an activity is voluntary or involuntary; whether effects are immediate or delayed; whether alternatives are available; how well the risks are known; whether an item is essential or a luxury; whether the risk is encountered inside or outside of the workplace; whether the risk is common or especially dread; whether the average person is affected or only sensitive individuals; whe-
REVIEW OF KEY CONCEPTS, ASSUMPTIONS, AND DECISIONS 63 ther a product is used as intended or is likely to be misused; and whether the consequences are reversible or irreversible (Lowrance 1976; Slovic 1987). The concept of acceptable risk, with its assorted nomenclature, has evolved and changed over the last few decades. The subcommittee presents a review in Appendix B that describes how various institutions and authors have defined acceptable risk as a concept applied to chemical products; it aims to distinguish between the scientific elements and value judgments. Both RD-230 and TG-230 state that the Armyâs acceptable cancer risk is 1 Ã 10-4 and adjustments were made to some of the guidelines for carcino- gens to ensure that the MEGs for carcinogens were based on the selected risk level. TG-230 indicates that the acceptable risk level is subject to change depending on the needs and characteristics of specific missions. The selected risk value for deployed military personnel falls within the range used by U.S. regulatory organizations and some international groups and is much lower than that applied to the nonmilitary workforce in the United States. This allows for some flexibility for situations involving repeated or multiple deployments where career-long exposure could lead to excess cancer risk greater than 1 Ã10-4. By establishing a 1-year guideline based on a target excess lifetime risk of 1 Ã10-4, it is reasonable to expect that career-long risk would not exceed 1 Ã10-3. Thus, 1 Ã 10-4 is consistent with DOD policy that âacceptable exposure measures and limits shall be derived from use of the risk management processâ (DOD Instruction 6055.1, August 1998). The limit is reasonable in terms of protecting human health and also is flexible, allowing commanders to balance mission objec- tives and health protection. One issue involving acceptable levels of risk bears discussion. Military documentation provides little usable guidance on variations in exposures where some of the exposure concentrations exceed the acceptable risk threshold for some length of time. Dealing with those fluctuations requires an understanding of the underlying toxicological and epidemiological infor- mation on which the risk estimates are based and of the parameters and outputs of the low-dose model or models employed. CONSIDERATION OF IMMEDIATE AND LONG-TERM HEALTH EFFECTS Army policy (U.S. Department of the Army 2001) dictates that a pro- cess be in place to
64 TECHNICAL GUIDES ON ASSESSING AND MANAGING CHEMICAL HAZARDS â¢ âEnsure that commanders are aware of and consider the FHP-OEH [force health protection occupational and environmental health] risks cre- ated by OEH exposures (both long-term and short-term) during all phases of military operations, and over the broad spectrum of military activities.â â¢ âReduce the OEH exposures to as low as practicable to minimize short-term and long-term health effects in personnel within the context of the full spectrum of health and safety risks confronting the deployed person- nel and consistent with operational risk management principles.â Thus, in reviewing the Armyâs technical guides, the subcommittee was asked to evaluate the balance of emphasis between health effects produced immediately or soon after chemical exposures and possible long-term or delayed health effects (e.g., cancer). The need for considering immediate and long-term health effects is discussed in both TG-248 and TG-230 as part of the guidance on MEG development and implementation. The two types of health considerations for chemical risks are characterized as symptoms occurring either âduringâ or âafterâ the mission, as shown in Chapter 2, Table 2-2, which provides guidance on how to rank a chemical hazardâs severity. Because military operational risk management (ORM) focuses on mission success, that guid- ance table was designed to categorize health effects that might occur during the mission and could affect the functional capabilities of personnel (i.e., medical threats) as of greater risk than delayed health effects. The subcommittee found that for mission-risk assessment, it is gener- ally necessary to focus the commanderâs attention on short-term effects. The guidance provided in TG-248 for occupational and environmental health and endemic disease (OEH/ED) hazard-severity ranking and TG- 230âs chemical hazard-ranking scheme appropriately give greater emphasis to short-term effects. In TG-248, post-mission symptoms are categorized as either having ânegligibleâ or âmarginalâ effects on the mission, depend- ing on the percentage of exposed personnel projected to exhibit the symp- toms. For chemical exposures, TG-230 classifies post-mission symptoms resulting from exposures where MEGs (or CCEGs, as recommended by the subcommittee) either were not exceeded or were only minimally exceeded as health threats posing no threat or a negligible threat to the mission. However, the classification guidance given in TG-230 is limited to health outcomes that occur in 0-10% of personnel, clearly below any mission critical threshold identified in Tables 2-1 to 2-4. No explicit guidance is provided on how to classify situations involving delayed-onset or chronic illness that might occur in a larger percentage of the deployed population
REVIEW OF KEY CONCEPTS, ASSUMPTIONS, AND DECISIONS 65 (e.g., chronic lung or liver disease that might result from acute exposure to lung or liver toxicants, respectively). For the purposes of force health protection, short- and long-term health effects should be considered equally, because the goal is to protect the health of each individual that might be exposed. The example summary table provided in TG-230âs Appendix F illustrates that USACHPPMâs intent is that short- and long-term health information will be provided to decision makers simultaneously with mission-risk information. That intent should be made more explicit in the main body of TG-230. Finally, the subcommittee noted that cancer is highlighted in the guid- ance as the most serious delayed outcome of chemical exposures, whereas other possible chronic or delayed maladies and dysfunctions are not as thoroughly addressed, if addressed at all. That implies that cancer is the only long-term consequence of concern to the military. To rectify this deficiency, attention should be given to other chronic or delayed-onset effects, such as effects on the respiratory system, the immune system, repro- duction, development, and kidney function. In the future, the subcommittee expects that some consideration should also be given to assessing indirect effects of exposure, such as psychologi- cal or morale effects, which could affect health and mission effectiveness. Because other aspects of deployment also cause or contribute to those stresses (e.g., hostile environment, separation from family), it might be appropriate that guidance be developed at the operational risk management level. AGGREGATE EXPOSURE AND CUMULATIVE RISK EPA defines aggregate exposure as exposure to a single chemical by multiple pathways (e.g., air, food, drinking water) and multiple routes of exposure (inhalation, oral, and dermal) (EPA 2001b). In TG-230, USACH- PPM considers exposures from each environmental medium (air, water, and soil) independently and gives little consideration to aggregate exposures from multiple pathways. For the purposes of CCEGs, it is probably unnec- essary to aggregate the risks from multiple media because air is likely to be the dominant source of exposure. However, it is important for force health protection that some consideration is given to aggregate exposures. (See Chapter 5 for further discussion.) Cumulative risks from exposures to more than one chemical or to multi- ple hazards are also important considerations. Cumulative risk assessment
66 TECHNICAL GUIDES ON ASSESSING AND MANAGING CHEMICAL HAZARDS involves studying the accumulation (over time, across sources, across routes, etc.) of stressors or exposures that can cause adverse effects and integrating the possible effects of those stressors to estimate and character- ize the cumulative risk they pose (EPA 2001c). NRC (2000b) noted that âTroops during deployment could become exposed to a number of threats simultaneously. Exposures that are individually acceptable without appre- ciable risk might not be so when several are experienced together, and the question of interactions among agents looms particularly large for deploy- ment risk assessment.â TG-230 assumes that the toxicity of a mixture of chemicals that have similar modes of action will be equal to the sum of the weighted dose toxicities of the individual chemicals. Although that is gen- erally an accepted practice, it is unclear how cumulative risk should be assessed when multiple hazards are present. RD-230 states that âTG-230 provides a general approach to address the potential for additive or even synergistic reactions when there are multiple chemical hazards present ... [as] exemplified through various Hypothetical Case Studies presented in 230 Appendix F in TG.â Indeed, three of the seven hypothetical case stud- ies (CS-3, CS-6, and CS-7) describe exposure scenarios that involve multi- ple chemicals, multiple potential routes of exposure, and/or multiple expo- sure locations. However, the potential difficulties in conducting compara- tive analyses of mixtures of threats are not illustrated by these cases studies, because each case described involves risks that clearly are dominated by a single risk source. TG-230 does not provide guidance on how cumulative risks are to be assessed, other than that they should be considered qualitatively. The sub- committee examined a number of chemicals whose similar lethal effects would at least summate, but found that it was impossible to identify that type of potential interaction from the descriptions of symptoms and target organs provided in RD-230. For example, both hydrogen cyanide and hydrogen sulfide can cause death by terminally inhibiting oxidative metabo- lism, but the look-up tables do not indicate that potential. For the purposes of mission-risk assessment, problems caused by the categorical analytic scheme are compounded by the lack of a systematic procedure to combine the multiple corresponding categorical levels of haz- ard severity and hazard probability that could be involved during opera- tions. Any such procedure is likely to be too cumbersome to be practical and to yield results of questionable consistencyâparticularly in cases that involve multiple sources of relatively high risk from chemical exposures. An alternative procedure that could facilitate comparative analyses is dis- cussed in Chapter 4 and in Appendix E.
REVIEW OF KEY CONCEPTS, ASSUMPTIONS, AND DECISIONS 67 For the purposes of force health protection, it is important to consider risks from exposures to multiple chemicals. This will require assessing, to the extent feasible, whether the toxicities of chemicals found in mixtures produce additive, less than additive, antagonistic, or synergistic effects. That might be accomplished in the short-term by flagging compounds that are likely to be present in mixtures and in combinations that might be of concern. Chemicals frequently affect the same organs by different mecha- nisms, but for the sake of simplicity, similar pathologies often are consid- ered to share a common mechanism. Chapter 5 expands on the cumulative risk considerations for MEGs. EXPOSURE ASSESSMENT Reliable identification and assessment of chemical exposures is a key component of the application and interpretation of MEGs and CCEGs. Exposure assessment is the determination or estimation (qualitative or quan- titative) of the magnitude, frequency, duration, and route of exposure to a particular chemical (57 Fed. Reg. 22888 ). It involves the identifica- tion, measurement, and modeling of exposures to potential chemical haz- ards. Exposure assessment is discussed generally in TG-230 (particularly in Appendix F, âHypothetical Case Studiesâ) and in TG-248 (which ex- pands upon the METT-TC considerations of mission, enemy, terrain, troops, time, and civilians), but no comprehensive guidance is provided on what exposure metrics (e.g., averaging times, peaks) the Army plans to use or how to develop and apply an exposure-assessment plan. The subcommit- tee was informed that more specific guidance is currently being developed by USACHPPM in a separate technical guide (A Soldierâs Guide to Envi- ronmental and Occupational Field Sampling for Military Deployment). For deployments, the subcommittee envisions that exposure assess- ments would, in general, involve identifying potential chemical hazards by using available classified and unclassified site-specific information; assess- ing the level of potential exposures by using sampling data, modeling, or assumptions; comparing exposure estimates with CCEGs to assess potential risks to the mission and to determine what risk trade-offs are necessary to accomplish the specific mission; and comparing exposure estimates with MEGs to assess potential health hazard and, in the event that some health trade-offs must be made, to determine what types of follow-up management actions are necessary to fulfill the militaryâs force health protection respon- sibilities (e.g., documentation of exposures in medical records, medical monitoring).
68 TECHNICAL GUIDES ON ASSESSING AND MANAGING CHEMICAL HAZARDS Although it is clear that TG-230 was not designed to provide explicit guidance on how to conduct exposure assessments, the subcommittee be- lieves it is worthwhile to go over some of the general requirements for an exposure-assessment plan. Such a plan should include, but should not be limited to, obtaining quantitative data from monitoring and modeling; de- veloping a sampling plan; and establishing a decision logic that determines what actions to take based on the outcome of the exposure assessment (i.e., when to conduct additional sampling, when to require medical monitoring). The sampling plan should address the decision indicators for additional or reduced sampling frequency; the number and location of air, water, and soil samples; how to obtain representative and valid sampling results; and the need for continuous monitoring in some instances. Whenever relevant, decision-making aids, such as check lists or matrices, should be used. Sta- tistical treatment and interpretation of data should be an integral component of the exposure-assessment guidance. For example, the large confidence limits associated with small data sets and the log-normal distributions typi- cally found in occupational and environmental data sets increase the proba- bility of misclassifications (i.e., concluding that exposures are acceptable when in fact they are unacceptable). Bayesian decision analysis is well suited to classifying data from limited data sets into one of several catego- ries (e.g., clearly acceptable, marginally acceptable, marginally unaccept- able, or clearly unacceptable) and could be used to develop decision logics for both force health protection and course-of-action decisions (Hewett 2003a,b). This technique requires limited quantitative exposure data in combination with simple professional judgment, previous analyses of his- torical exposure data, or exposure modeling predictions. The calculations are complex and require the use of programmable software; however, the user need only enter the exposure data and select an initial decision histo- gram. The end result is a final decision histogram of the probabilities that exposures occur in each of the exposure categories. Army guidance should clarify the appropriateness of different exposure metrics for comparison with MEGs and CCEGs, and the differences in sampling methods, frequency, and intensity between exposure assessments conducted to support mission-risk assessments, those conducted to inform force health protection decisions, and others meant to provide documenta- tion of personnel exposures to chemicals. Exposure assessments used for mission-risk assessment are particularly important, because time, access to external support, and data are more likely to be minimal in those situations. Identification and selection of appropriate risk-management techniques and the factors affecting the decision to proceed with their adoption should be included.
REVIEW OF KEY CONCEPTS, ASSUMPTIONS, AND DECISIONS 69 Force health protection exposure documentation might require sampling when there is little or no expectation of excess exposure. In other situa- tions, several samples might be collected to verify worse-case exposures. Depending on the outcomes of exposure assessments, appropriate follow-up actions might include documentation of results with no further action, addi- tional sampling, provision of personal protective equipment, substitution of materials or equipment, or cancellation of activity. Implementing sound industrial-hygiene practices that include documenting exposures and keep- ing records is an example of appropriate follow-up action. Although some of the components of an exposure-assessment plan exist in the guidance, there is no logical, overall plan that indicates the philoso- phy, purpose, and principles of exposure assessment, particularly outlining the different approaches to exposure assessment for the purposes of force health protection and course-of-action decisions. If assembled, evaluated, and supplemented, the components already available would be valuable in developing a comprehensive exposure-assessment plan in circumstances that allow more thorough evaluations. Situations might arise in which the limits of detection of available mon- itoring instruments are above the levels of concern for personnel exposures. Lists of the chemical agent detection technologies and the manufacturers of fielded instruments have been compiled in various documents (Brletich et al. 1995; IOM 1999; Jackson et al. 1998; Lewis and Lorenz 1998; OâHern et al. 1997). The methods used for fixed-facility chemical warfare agent detection (mass spectrometry, gas chromatography, and Fourier transform infrared spectrometry) are not available in the field. The field technology currently available cannot provide the sensitivity and/or the rapid response necessary to protect troops from low concentrations of those agents. For example, for nerve agents GA, GB, GD, and VX, the minimal-effect air MEGs for 10 minutes to 24 hours are below the detection limits of handheld detectors (0.01 mg/m3), as are the 24-hour MEGs that predict significant health effects. Using exposure assessments to properly estimate risks requires a high degree of professional judgment on the part of preventive-medicine person- nel, as noted in TG-230: â¢ â[Trained preventive-medicine personnel] should be familiar with basic methods of exposure assessment of chemicals in the environment. ... Military health services personnel will need to use professional judgment when applying the standardized information in this guideâ (USACHPPM 2002a, p. 4).
70 TECHNICAL GUIDES ON ASSESSING AND MANAGING CHEMICAL HAZARDS â¢ âThe user should compare the guidelines with field sampling data or other (e.g., modeled) exposure data information. The interpretation of these comparisons will require professional judgmentâ (USACHPPM 2002a, p. 5). â¢ âThe process of assessing and characterizing health risks from chemical exposures inherently involves significant data limitations, uncer- tainty, variability, and professional judgmentâ (USACHPPM 2002a, p. 19). The level of professional judgment required for proper application of the MEGs and CCEGs makes it particularly important that preventive-medi- cine personnel receive comprehensive and adequate training in exposure assessment and risk management. The training should go beyond âhow toâ and âwhen and whereâ guidance; it should provide guidance on developing exposure-assessment plans consistent with the range of limiting conditions that are likely to be encountered and making risk-management decisions on the basis of exposure assessment outcomes. The latter issue is discussed further in Chapters 4 and 5. UTILITY FOR DECISION MAKERS The subcommittee was asked to evaluate the utility of TG-248 and TG- 230 for decision makers, some of whom might not be knowledgeable about toxicology or the risk-assessment process. Because it was the subcommit- teeâs understanding that the guides will be used in the field by a subordinate to the decision maker and not the decision maker, the subcommittee inter- preted this task as asking if (1) an untrained individual could use the guides to characterize chemical risks appropriately and (2) if the risk characteriza- tion developed from using the guides would be useful to the decision maker. The first task seems to be in direct conflict with the statement in TG-230 that the guide is ânot intended for use by untrained personnel or as a substi- tute for having trained preventive medicine personnel on-site or in the the- ater.â TG-230 outlines an evaluative process that relies on the use of look- up tables, worksheets, and examples of how to apply those tools. The sub- committee found that TG-230 provides systematic guidance on how to evaluate potential chemical risks, but some of the decisions that must be made while using the guidance require the subjective judgment of experi- enced personnel. Therefore, some training in preventive medicine, toxicol- ogy, and risk assessment is necessary for TG-230 to be used effectively. The second element of the question is whether the products of TG-230 guidance are easy for the decision makers to understand so they can prop-
REVIEW OF KEY CONCEPTS, ASSUMPTIONS, AND DECISIONS 71 erly consider the occupational and environmental health effects of chemical risks. The subcommittee concluded that the use of the ORM risk-assess- ment matrix in TG-230 effectively facilitates the communication of chem- ical-hazard risks in terms that are understandable to military decision mak- ers. However, as noted in Chapter 2, TG-230 should be refined to make it consistent with TG-248, primarily to ensure that chemical risks are charac- terized using the same ORM metric as other risks. Chemical mission-risk estimates based on MEGs are not equivalent to other ORM risks because the MEGS are health-protection guidelines and not casualty estimates. CCEGs that predict casualty rates are necessary for appropriate course-of- action decision making. RECOMMENDATIONS This section summarizes the major recommendations made in this chap- ter on some of the key concepts and assumptions made in developing TG- 248, TG-230, and RD-230. The text itself should be consulted for more thorough discussion of these issues and for several other recommendations that are of secondary importance. â¢ The application of UFs in setting exposure values to assess mission risks and health risks needs careful consideration. UFs should only be applied if they improve the accuracy of the exposure guideline for its in- tended purpose. Furthermore, thoughtful consideration will be needed to determine how to handle some of the complex issues involved in determin- ing UFs, especially the UF for interspecies extrapolation, which involves pharmacokinetic and pharmacodynamic considerations. â¢ Immediate and long-term health effects should be considered when making course-of-action decisions. Greater weight should be given to immediate effects in the mission-risk assessment, and short- and long-term health consequences should be weighted equally in the health-risk assess- ment. USACHPPM needs to develop a more comprehensive set of guid- ance on how preventive-medicine personnel should convey long-term health information to commanders and what actions the Army should take to address those threats (e.g., when follow-up medical monitoring should be required). â¢ Deployed populations should be considered as healthier than the general population, and pre-existing health conditions do not need to be factored into the exposure guidelines. A UF for interindividual variation in susceptibility among humans should be applied to develop CCEGs only if
72 TECHNICAL GUIDES ON ASSESSING AND MANAGING CHEMICAL HAZARDS its application improves the accuracy of the CCEGs to predict toxic response by better accounting for evidence that a subpopulation within the deployed population is more sensitive than the group(s) used to obtain experimental or epidemiological data upon which that CCEG is based. â¢ TG-230 indicates that the embryo and fetus are of concern, so the current set of MEGs should be screened to assess whether they are protec- tive of the embryo and fetus. â¢ Comprehensive exposure-assessment guidance should be compiled from existing sources and linked with TG-230 to support preventive-medi- cine personnel in developing exposure-assessment plans. The guidance should include information on monitoring and modeling, developing a sampling plan, and establishing a decision logic for management actions (discussed further in Chapter 4 and 5). The guidance should explain the differing approaches needed to support course-of-action decisions and to inform force health protection efforts. â¢ When CCEG and MEG values are below field detection capabili- ties, research and development support should be provided to aid in the development of more sensitive and reliable field detection equipment. This is particularly important in the case of chemical warfare agents. â¢ Guidance on how to consider risks from exposure to multiple chem- icals, particularly in instances where there is no dominant risk source, is necessary. That will require assessment and documentation, to the extent feasible, of whether the toxicities of chemicals found in mixtures produce additive, less than additive, or synergistic effects. â¢ Because some of the decisions that must be made while using the guidance tools of TG-230 require subjective evaluation, it is important that personnel using the guidance have some training in preventive medicine and risk assessment. REFERENCES AAFA (Asthma and Allergy Foundation of America). 2003. Asthma and Allergy Founda- tion of America. [Online]. Available: http://www.aafa. org/ AIHA (American Industrial Hygiene Association). 1988. Formaldehyde Emergency Re- sponse Planning Guidelines. Fairfax, VA: AIHA Press. AIHA (American Industrial Hygiene Association). 1989. Oleum, Sulfur Trioxide, and Sulfuric Acid Emergency Response Planning Guidelines. Fairfax, VA: AIHA Press. AIHA (American Industrial Hygiene Association). 1997. Acrylonitrile Emergency Re- sponse Planning Guidelines. Fairfax, VA: AIHA Press. Brletich, N.R., M.J. Waters, G.W. Bowen, and M.F. Tracy. 1995. Worldwide Chemical Detection Equipment Handbook. Gunpowder Branch Aberdeen Proving Ground, MD: Chemical and Bio- logical Defense Information Analysis Center.
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