1
Introduction

Submariners live in isolated, confined, and often crowded conditions when at sea. They must adjust to an 18-h day (6 h on duty and 12 h of training, other related activities, and free time) and are continuously exposed to air contaminants in their environment. To protect submariners from the potential adverse health effects associated with air contaminants, the U.S. Navy has established 1-h and 24-h emergency exposure guidance levels (EEGLs) and 90-day continuous exposure guidance levels (CEGLs) for a number of the contaminants.

In December 1995, the Navy began reviewing and updating submarine exposure guidance levels (Crawl 2003). Because the National Research Council (NRC) Committee on Toxicology (COT) had previously reviewed and provided recommendations for those and other types of exposure guidance levels (NRC 1984a,b,c; 1985a,b; 1986a; 1987; 1988a; 1994; 1996a,b; 2000a,b,c; 2002a,b; 2003), the Navy requested that COT review or if necessary develop EEGLs and CEGLs for 21 chemical substances. As a result of the Navy’s request, NRC convened a committee that reviewed those 21 chemicals and published two reports on them (NRC 2007, 2008). As a follow-on activity, the Navy requested review of an additional five chemicals, and NRC convened a second Committee on Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants in 2008.

THE COMMITTEE’S CHARGE

Members of the committee were selected for their expertise in inhalation toxicology, neurotoxicology, regulatory toxicology, veterinary pathology, respiratory pathology, pharmacokinetics, pulmonary and occupational medicine, and human-health risk assessment. See Appendix A for biographic information on the committee. The committee was asked to review the Navy’s current and proposed 1-h and 24-h EEGLs and 90-day CEGLs for selected submarine contami-



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1 Introduction Submariners live in isolated, confined, and often crowded conditions when at sea. They must adjust to an 18-h day (6 h on duty and 12 h of training, other related activities, and free time) and are continuously exposed to air contami- nants in their environment. To protect submariners from the potential adverse health effects associated with air contaminants, the U.S. Navy has established 1- h and 24-h emergency exposure guidance levels (EEGLs) and 90-day continu- ous exposure guidance levels (CEGLs) for a number of the contaminants. In December 1995, the Navy began reviewing and updating submarine exposure guidance levels (Crawl 2003). Because the National Research Council (NRC) Committee on Toxicology (COT) had previously reviewed and provided recommendations for those and other types of exposure guidance levels (NRC 1984a,b,c; 1985a,b; 1986a; 1987; 1988a; 1994; 1996a,b; 2000a,b,c; 2002a,b; 2003), the Navy requested that COT review or if necessary develop EEGLs and CEGLs for 21 chemical substances. As a result of the Navy’s request, NRC convened a committee that reviewed those 21 chemicals and published two re- ports on them (NRC 2007, 2008). As a follow-on activity, the Navy requested review of an additional five chemicals, and NRC convened a second Committee on Emergency and Continuous Exposure Guidance Levels for Selected Subma- rine Contaminants in 2008. THE COMMITTEE’S CHARGE Members of the committee were selected for their expertise in inhalation toxicology, neurotoxicology, regulatory toxicology, veterinary pathology, respi- ratory pathology, pharmacokinetics, pulmonary and occupational medicine, and human-health risk assessment. See Appendix A for biographic information on the committee. The committee was asked to review the Navy’s current and pro- posed 1-h and 24-h EEGLs and 90-day CEGLs for selected submarine contami- 8

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9 Introduction nants and, if possible, to develop EEGLs and CEGLs for selected chemicals that do not have existing or proposed levels. The committee was also asked to iden- tify data gaps and to make recommendations for future research. Specifically, the Navy asked the committee to review guidance levels for acetaldehyde, hy- drogen chloride, hydrogen fluoride, hydrogen sulfide, and propylene glycol dini- trate. See Appendix B for a verbatim statement of task. POPULATION CHARACTERISTICS An estimated 30,000 submariners are on active duty in the U.S. Navy (Cassano 2003). Permanent crew members on U.S. submarines are all male and are 18-48 years old. Before entry into the submarine service, candidates receive comprehensive physical and psychologic examinations and are rejected if any major medical problems—such as heart disease, asthma, or chronic bronchitis— are noted (U.S. Navy 1992, 2001). Submariners are also required to undergo a complete physical examination every 5 years (Capt. D. Molé, U.S. Navy, per- sonal commun., May 28, 2003); they may be disqualified from submarine duty if any medical problems are noted at that time or during active duty (Cassano 2003). Thus, the population that serves on U.S. submarines is, in general, quite healthy. Studies that have evaluated mortality patterns in U.S. submariners support the conclusion that submariners are healthy. Charpentier et al. (1993) examined a cohort of 76,160 submariners who served on U.S. nuclear-powered submarines during the period 1969-1982. They compared mortality in the submariners with that in the general adult male population of the United States and found that the standardized mortality ratio (SMR) for total mortality was significantly less than 1.1 The SMR was also significantly lower than that expected in a military popu- lation. The SMRs for specific causes of mortality were also less than 1. SMRs exceeded 1 for only two causes: malignant neoplasms of the central nervous system (SMR, 1.03) and motor-vehicle accidents (SMR, 1.06). The results re- ported by the study authors were supported by a study of Royal Navy submarin- ers, who must meet stringent physical requirements similar to those of the U.S. Navy (Inskip et al. 1997). Morbidity patterns in U.S. Navy submariners also indicate a healthy popu- lation. Thomas et al. (2000) evaluated the rates of medical events in crews on 136 submarine patrols over 2 years (1997-1998). Injury was the most common medical-event category, followed by respiratory illness (primarily upper respira- tory infections) and then skin problems, such as minor infections and ingrown toenails. Other medical events included ill-defined symptoms, infectious dis- eases, digestive disorders, ear and eye complaints, and musculoskeletal condi- 1 An SMR indicates whether mortality in a given population is greater (SMR > 1) or less (SMR < 1) than that in a comparison population.

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10 Exposure Guidance Levels for Selected Submarine Contaminants tions. The categories just listed account for about 90% of the 2,044 medical events reported. Although recent data indicate that U.S. submariners are a healthy popula- tion, some might be sensitive to particular air contaminants because of genetic predisposition or conditions arising during active duty. For example, Sims et al. (1999) reported that asthma led to the disqualification each year of 0.16% of the active-duty personnel serving in the Atlantic Fleet Submarine Force (the authors considered the asthma cases to be mild). Tobacco smokers might be more or less sensitive to some air contami- nants. Smoking on U.S. submarines is permitted only in specified areas. The percentage of U.S. submariners who smoke is difficult to estimate because no broad survey has been conducted. Sims et al. (1999) estimated a prevalence of smoking of 36% on the basis of data on eight submarines. However, Thomas et al. (2000) estimated that the prevalence might be as low as 22% on the basis of survey data collected from one submarine in 1997. The Navy has indicated that the percentage of submariners who smoke most likely ranges from 15% to 30% (Cmdr. W. Horn, U.S. Navy, personal commun., August 7, 2003). However, smoking policies on board submarines vary because they are determined by the commanding officer. One other aspect of the population that could affect its sensitivity to chemical exposure is consumption of alcoholic beverages. However, no alcohol is allowed on board a submarine, so there is no expected consumption of alco- holic beverages while the crew is on board (Cmdr. G. Chapman, U.S. Navy, personal commun., May 29, 2009). THE SUBMARINE ENVIRONMENT The U.S. submarine fleet is composed mostly of two types of submarines (Thomas et al. 2000). Table 1-1 provides some distinguishing characteristics of the crews and patrols of the two submarine types. When submerged, a submarine is an enclosed and isolated environment. Submariners work, eat, and sleep in that environment and potentially are ex- posed to air contaminants 24 h/day. A submarine differs from typical occupa- tional settings in which workers have respites from workplace exposures at the end of their shifts or workweeks. Operation of a closed vessel can lead to accumulation of air contaminants (NRC 1988b). Major sources of air contaminants on a submarine include ciga- rette-smoking, cooking, and the human body. Other sources include control equipment, the power train, weapons systems, batteries, sanitary tanks, air- conditioning and refrigeration systems, and a variety of maintenance and repair activities. Several onboard methods are used to maintain a livable atmosphere and re- move air contaminants (NRC 1988b). Oxygen generators add oxygen to the air

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11 Introduction TABLE 1-1 Characteristics of Crew and Patrols for U.S. Navy Nuclear- Powered Submarines Number and Size of Typea Crew Typical Patrol Nuclear-powered attack 1 designated crew of Irregular intervals between patrols; submarines (SSN) 130 men patrols of variable length Nuclear-powered ballistic- 2 rotating crews of Regularly scheduled patrols; 90- missile submarines (SSBN) 160 men each day cycle between ship and shore; patrols over 60 days long a Note that there are three classes of attack submarines—Los Angeles, Seawolf, and Virginia—and one class of ballistic-missile submarines—Ohio. There are also two deep- diving specialized research submarines (one nuclear-powered and the other diesel- powered) that are in a class of their own (Capt. D. Molé, U.S. Navy, personal commun., January 15, 2004). Source: Information from Thomas et al. 2000. by electrolyzing seawater. The hydrogen that is generated in the process is dis- charged to the sea. Monoethanolamine scrubbers are used to remove carbon di- oxide from the air. Carbon monoxide that is generated primarily by cigarette- smoking and hydrogen that is released in battery-charging are removed by a carbon monoxide–hydrogen burner that catalytically oxidizes the two compo- nents to carbon dioxide and water, respectively; hydrocarbons are also oxidized by this system. Activated-carbon filters help to remove high-molecular-weight compounds and odorants, and electrostatic precipitators help to remove particles and aerosols. Vent-fog precipitators are used in the engine room to remove oil mists generated there. Other means of minimizing air contaminants include re- stricting the materials that can be brought on board and limiting the types of activities, such as welding, that can be conducted at sea. When the submarine is submerged, air is recirculated in a closed-loop sys- tem. The system is composed of the forward-compartment air-circulation system and the engine-compartment air-circulation system (R. Hagar, Naval Sea Sys- tems Command, personal commun., April 2, 2003). Figure 1-1 is a generalized schematic of a nuclear-powered attack submarine. The forward-compartment air-circulation system contains most of the air-purification equipment and oxy- gen generators and is designed to condition the air to 80°F and 50% relative humidity. The forward compartment is divided into zones; the fan room serves as the mixing chamber. Stale air from the boat is exhausted to the fan room, and the fan room supplies treated air to the boat. The engine-compartment air- circulation system provides heating, cooling, and air distribution within the en- gine room and is designed to maintain its air temperature below 100°F. Electro- static precipitators and other filters in this room treat its air. Air from the engine room is exhausted directly to the fan room, which supplies conditioned air di- rectly to the engine room.

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12 FIGURE 1-1 Generalized schematic of a nuclear-powered attack submarine. Source: Adapted from image courtesy of the Smithsonian/NMAH Transportation.

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13 Introduction Special variations in the exhaust airflow path described above exist (R. Hagar, Naval Sea Systems Command, personal commun., April 2, 2003). Air discharged from the carbon monoxide–hydrogen burners and the carbon dioxide scrubbers is vented directly to the fan room. Many electronic cabinets have fan systems that also vent directly to the fan room, and air from the laundry dryers passes through lint screens and then to the fan room. About 50% of the air vented to the fan room passes through electrostatic precipitators, and air from the galley, scullery, pantry, and water closets goes through activated-charcoal filters before venting to the fan room. Cooking grease is removed from the range and fryer hoods by centrifugal force. The central atmosphere monitoring system (CAMS) of the submarine uses an infrared spectrometer to measure carbon monoxide and a mass spectrometer to measure oxygen, nitrogen, carbon dioxide, hydrogen, water vapor, and Freons 11, 12, and 114 (NRC 1988b). A newer version of CAMS (CAMS MK II) can monitor the following trace species: acetone; aliphatic hydrocarbons (sum of masses 57, 71, 99, and 113); aromatic hydrocarbons (sum of masses 91, 105, 119, 133, and 147); benzene; Freons 12, 114, and 134a; isobutylene; methanol; methyl chloroform; silicone; and trichloroethylene. Fan-room air is monitored continuously, and air in other onboard locations is analyzed on a rotating basis. Portable devices are routinely used to monitor submarine air (Hagar 2003; NRC 1988b). Photoionization detectors monitor total hydrocarbon concentra- tions, although they are not used in submarines equipped with the newer version of CAMS. A portable oxygen detector verifies oxygen concentrations weekly. Colorimetric detector tubes are used weekly to measure concentrations of ace- tone, ammonia, benzene, carbon dioxide, carbon monoxide, chlorine, hydrazine, hydrochloric acid, methyl chloroform, monoethanolamine, nitrogen dioxide, ozone, sulfur dioxide, toluene, and total hydrocarbons. During battery-charging, portable detectors are also used to monitor hydrogen concentrations. Suspected fluorocarbon or torpedo-fuel leaks are assessed with portable devices that have photoionization detectors. Retrospective passive monitoring of the submarine air provides 30-day time-weighted average concentrations of volatile organic com- pounds, ozone, acrolein, aldehydes, amines, and nitrosamines. Exposure data on compounds addressed in this report are presented in the individual chapters. THE COMMITTEE’S APPROACH TO ITS CHARGE The committee reviewed relevant human and animal data and used data- selection criteria described in Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals (NRC 2001). Specifically, the committee’s approach to data selection included the following elements:

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14 Exposure Guidance Levels for Selected Submarine Contaminants • Whenever possible, primary references (published or unpublished study reports) were used to derive exposure guidance levels. Secondary references were used to support the levels derived and the selection of critical end points. • Whenever possible, studies that followed accepted standard scientific methods were selected as key studies for deriving exposure guidance levels. Evaluation of study quality required the professional expertise and judgment of the committee. • Inhalation-exposure studies were used to derive exposure guidance lev- els. Data on other exposure routes (oral and dermal) were considered, especially in evaluating pharmacokinetics, tissue dose, metabolism, and mechanisms of toxicity. • Human studies were preferred for deriving exposure guidance levels. The committee considered human data from accidental exposures, experimental studies, and epidemiologic studies to be valuable in determining the effects of chemical exposure. When epidemiologic and human experimental studies were available, a preference typically was given to the latter because these were con- ducted in a controlled laboratory setting and allowed measurement of personal exposure and evaluation of end points relevant to derivation of exposure guid- ance levels. The committee recognizes that one potential problem with experi- mental studies is the statistical power of a study to detect an effect in the small number of subjects typically used. That design problem often exists in studies of humans or large animals, such as nonhuman primates and dogs. However, the committee did not set a threshold for statistical power, for two reasons. First, data presented in manuscripts or technical reports were often inadequate to al- low the committee to perform independent calculations to determine the power of an experiment. Second, derivation of the EEGLs and CEGLs was never based solely on a single study; multiple key studies were always supported by other human experimental studies, epidemiologic studies, or animal studies (see last bulleted item). To the best of the committee’s knowledge, the data used were not obtained from uninformed or coerced subjects. • When high-quality human data were not available, standard laboratory animal studies were used to derive exposure guidance levels. The animal species used were those on which there were historical control data and those which were most relevant to humans. • A weight-of-evidence approach was used to select key studies that en- sured that selected data were consistent with the overall scientific database and incorporated what was known about the biologic effects of a chemical on perti- nent organ systems. The committee followed basic procedures provided by Criteria and Methods for Preparing Emergency Exposure Guidance Level (EEGL), Short- Term Public Emergency Guidance Level (SPEGL), and Continuous Exposure Guidance Level (CEGL) Documents (NRC 1986b) but also considered the

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15 Introduction procedures for developing similar exposure levels provided in more recent re- ports (NRC 1992, 2001). The committee evaluated chemicals individually and did not address exposures to chemical mixtures. It recommends that empirical data that characterize mixtures found in submarine air be evaluated when they become available. It considered only health end points relevant to healthy young men on the assumption that women do not serve as permanent crew on subma- rines. In deriving EEGLs and CEGLs, the committee assumed that the confined conditions on a submarine keep the crew from achieving maximal exercise. It also assumed that a submarine is operated at an internal pressure near 1 atm. The specific approaches adopted by the committee for developing EEGLs and CEGLs are outlined below. Emergency Exposure Guidance Levels NRC (1986b) defines EEGLs as ceiling concentrations (concentrations not to be exceeded) of chemical substances that will not cause irreversible harm to crew health or prevent the performance of essential tasks, such as closing a hatch or using a fire extinguisher, during rare emergency situations that last 1-24 h. Exposures at the EEGLs may induce reversible effects, such as ocular or up- per respiratory tract irritation, and they are acceptable only in emergencies when some discomfort must be endured. After 24 h of exposure, CEGLs would apply. To develop 1-h and 24-h EEGLs, the committee reviewed relevant human and animal toxicity data and considered all health end points reported. The EEGLs were based on acute or short-term inhalation and ocular-irritation data, and the most sensitive end points were emphasized. The committee considered conducting benchmark-dose or benchmark-concentration modeling, but the datasets were often not amenable for doing so, and points of departure were based on lowest observed-adverse-effect levels (LOAELs) or no-observed- adverse-effect levels (NOAELs) from human or animal studies. In deriving EEGLs, the committee used uncertainty factors that ranged from 1 to 10. Those factors accounted for interspecies differences (extrapolation from animal to human populations, if applicable), intraspecies differences (pos- sible variations in susceptibility that might be applicable to the healthy male population considered), extrapolations from a LOAEL to a NOAEL, and weak- nesses or critical gaps in the databases. The committee strove for consistency, but its overarching goal was a thorough case-by-case review of available data. Selection of uncertainty factors for each chemical reflects the committee’s best judgment of the data on toxicity and mode of action. Because an uncertainty factor of 3 represents a logarithmic mean (3.16) of 10, the committee considered the product of two uncertainty factors of 3 to equal a composite uncertainty fac- tor of 10, which is consistent with current risk-assessment practices (NRC 2001; EPA 2002).

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16 Exposure Guidance Levels for Selected Submarine Contaminants Continuous Exposure Guidance Levels NRC (1986b) defines CEGLs as ceiling concentrations of chemical sub- stances designed to prevent immediate or delayed adverse health effects or de- gradations in crew performance that might result from continuous chemical ex- posures lasting up to 90 days. To derive CEGLs, the committee used the basic approach outlined for developing EEGLs; relevant data were reviewed, sensitive end points evaluated, and appropriate uncertainty factors applied. The method differed only in that inhalation studies with repeated exposures were used, when available, as the primary basis of CEGL development. The effects of cumulative exposure were taken into account by using a weight-of-evidence approach. Carcinogenic Substances For known and suspected human carcinogens, the U.S. Department of De- fense sets military exposure levels to avoid a theoretical excess cancer risk of greater than 1 in 10,000 exposed persons (NRC 1986b). For chemicals that have been designated as known or suspected human carcinogens by the International Agency for Research on Cancer or by the U.S. Environmental Protection Agency, the committee evaluated the theoretical excess cancer risk resulting from exposure at the 90-day CEGLs. It considered deriving the cancer risk re- sulting from exposure at the 24-h EEGLs but concluded that such estimates would involve too much uncertainty. Additional information on cancer risk is provided in individual chapters as appropriate. The committee notes that COT typically has not proposed CEGLs for carcinogenic substances (NRC 1986b) but acknowledges that there is value in conducting such evaluations and has pro- posed 90-day CEGLs for known and suspected human carcinogens. Comparison with Other Regulatory Standards or Guidance Levels In its evaluations, the committee considered relevant inhalation exposure standards or guidance levels put forth by NRC and other agencies or organiza- tions. However, it notes that the submarine EEGLs and CEGLs differ from typi- cal public-health and occupational-health standards in three important ways. First, public-health standards are developed to protect sensitive populations— such as children, the elderly, and others with chronic health conditions who might be particularly sensitive—whereas EEGLs and CEGLs are developed for a healthy adult male population with little variation in physical qualifications. Second, occupational-health standards are designed for repeated exposure throughout a working lifetime on the assumption that workers are exposed 8 h/day, 5 days/week for a working lifetime. Submariners can be exposed 24 h/day with no relief from exposure during submergence. In a typical submariner’s ca- reer, a 10-year assignment to active sea duty would result in about 4.5-5 years of

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17 Introduction cumulative exposure in the enclosed submarine environment (Capt. V. Cassano, U.S. Navy, personal commun., December 16, 2003). Third, EEGLs allow for the development of reversible health effects that would not prevent the performance of essential tasks; such health effects might not be considered acceptable in set- ting conventional occupational-health or public-health exposure standards. The committee considered the submarine escape action levels (SEALs) and the spacecraft maximum allowable concentrations (SMACs) to be useful for comparison with EEGLs and CEGLs. SEALs are developed for disabled subma- rines and allow moderate, rather than only minimal, reversible effects (NRC 2002a). SMACs are probably the most comparable with EEGLs and CEGLs because SMACs are developed with similar criteria and address adverse effects in a healthy population in an isolated and confined environment. However, SMACs are developed for an older male and female population that experiences the conditions of microgravity during exposure. ORGANIZATION OF REPORT This report contains the committee’s rationale and recommendations with respect to EEGLs and CEGLs for acetaldehyde, hydrogen chloride, hydrogen fluoride, hydrogen sulfide, and propylene glycol dinitrate. Each chapter summa- rizes the relevant toxicologic and epidemiologic studies of a substance, selected chemical and physical properties, toxicokinetic and mechanistic data, and pub- lished regulatory and guidance levels for inhalation exposure. The committee’s recommendations for exposure guidance levels and for the research needed to define and support the recommendations are also provided. The chemical pro- files presented in this report are not comprehensive toxicologic profiles. The profiles focus on data that are particularly relevant to the derivation of EEGLs and CEGLs. References to recent authoritative reviews of the toxicology of some of the chemicals addressed in this report are provided. REFERENCES Cassano, V.A. 2003. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants. Presentation at the First Meeting on Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants, January 23, 2003, Washington, DC. Charpentier, P., A.M. Ostfeld, O.C. Hadjimichael, and R. Hester. 1993. The mortality of U.S. nuclear submariners, 1969-1982. J. Occup. Med. 35(5):501-509. Crawl, J.R. 2003. Review/Updating of Limits for Submarine Air Contaminations. Presen- tation at the First Meeting on Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants, January 23, 2003, Washington, DC. EPA (U.S. Environmental Protection Agency). 2002. A Review of the Reference Dose and Reference Concentration Processes. Final Report. EPA/630/P-02/002F. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC.

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18 Exposure Guidance Levels for Selected Submarine Contaminants [Online]. Available: http://oaspub.epa.gov/eims/eimscomm.getfile?p_download_ id=36836 [accessed Oct. 26, 2004]. Hagar, R. 2003. Submarine Atmosphere Control and Monitoring Brief for the COT Committee. Presentation at the First Meeting on Emergency and Continuous Ex- posure Guidance Levels for Selected Submarine Contaminants, January 23, 2003, Washington, DC. Inskip, H., M. Snee, and L. Styles. 1997. The mortality of Royal Navy submariners 1960- 89. Occup. Environ. Med. 54(3):209-213 . NRC (National Research Council). 1984a. Emergency and Continuous Exposure Limits for Selected Airborne Contaminants, Vol. 1. Washington, DC: National Academy Press. NRC (National Research Council). 1984b. Emergency and Continuous Exposure Limits for Selected Airborne Contaminants, Vol. 2. Washington, DC: National Academy Press. NRC (National Research Council). 1984c. Emergency and Continuous Exposure Limits for Selected Airborne Contaminants, Vol. 3. Washington, DC: National Academy Press. NRC (National Research Council). 1985a. Emergency and Continuous Exposure Guid- ance Levels for Selected Airborne Contaminants, Vol. 4. Washington, DC: Na- tional Academy Press. NRC (National Research Council). 1985b. Emergency and Continuous Exposure Guid- ance Levels for Selected Airborne Contaminants, Vol. 5. Washington, DC: Na- tional Academy Press. NRC (National Research Council). 1986a. Emergency and Continuous Exposure Guid- ance Levels for Selected Airborne Contaminants, Vol. 6. Washington, DC: Na- tional Academy Press. NRC (National Research Council). 1986b. Criteria and Methods for Preparing Emer- gency Exposure Guidance Level (EEGL), Short-term Public Emergency Guidance Level (SPEGL), and Continuous Exposure Guidance Level (CEGL) Documents. Washington, DC: National Academy Press. NRC (National Research Council). 1987. Emergency and Continuous Exposure Guidance Levels for Selected Airborne Contaminants, Vol. 7. Washington, DC: National Academy Press. NRC (National Research Council). 1988a. Emergency and Continuous Exposure Guid- ance Levels for Selected Airborne Contaminants, Vol. 8. Washington, DC: Na- tional Academy Press. NRC (National Research Council). 1988b. Submarine Air Quality: Monitoring the Air in Submarines. Washington, DC: National Academy Press. NRC (National Research Council). 1992. Guidelines for Developing Spacecraft Maxi- mum Allowable Concentrations for Space Station Contaminants. Washington, DC: National Academy Press. NRC (National Research Council). 1994. Spacecraft Maximum Allowable Concentra- tions for Selected Airborne Contaminants, Vol. 1. Washington, DC: National Academy Press. NRC (National Research Council). 1996a. Spacecraft Maximum Allowable Concentra- tions for Selected Airborne Contaminants, Vol. 2. Washington, DC: National Academy Press. NRC (National Research Council). 1996b. Spacecraft Maximum Allowable Concentra- tions for Selected Airborne Contaminants, Vol. 3. Washington, DC: National Academy Press.

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19 Introduction NRC (National Research Council). 2000a. Spacecraft Maximum Allowable Concentra- tions for Selected Airborne Contaminants, Vol. 4. Washington, DC: National Academy Press. NRC (National Research Council). 2000b. Submarine Exposure Guidance Levels for Selected Hydrofluorocarbons: HFC-236a, HFC-23, and HFC-404a. Washington, DC: National Academy Press. NRC (National Research Council). 2000c. Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 1. Washington, DC: National Academy Press. NRC (National Research Council). 2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals. Washington, DC: Na- tional Academy Press. NRC (National Research Council). 2002a. Review of Submarine Escape Action Levels for Selected Chemicals. Washington, DC: National Academy Press. NRC (National Research Council). 2002b. Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 2. Washington, DC: National Academies Press. NRC (National Research Council). 2003. Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 3. Washington, DC: National Academies Press. NRC (National Research Council). 2007. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 1. Washington, DC: Na- tional Academies Press. NRC (National Research Council). 2008. Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: Volume 2. Washington, DC: Na- tional Academies Press. Sims, J.R., P.M. Tibbles, and R.P. Jackman. 1999. A descriptive analysis of asthma in the U.S. Navy submarine force. Aviat. Space Environ. Med. 70(12):1214-1218. Thomas, T.L., T.I. Hooper, M. Camarca, J. Murray, D. Sack, D. Mole, R.T. Spiro, W.G. Horn and F.C. Garland. 2000. A method for monitoring the health of U.S. Navy submarine crewmembers during periods of isolation. Aviat. Space Environ. Med. 71(7):699-705. U.S. Navy. 1992. Submarine duty. Article 15-69 in Manual of the Medical Department, Change 107, October 29, 1992. U.S. Navy. 2001. Section III. Physical Standards for Appointment, Enlistment, or Induc- tion. Article 15-32 to 15-62 in Manual of the Medical Department, Change 116, U.S. Navy NAVMED P-117, June 11, 2001. [Online]. Available: http://www. vnh.org/Admin/MMD/Changes/MMDChanges.html [accessed March 15, 2004].