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Summary

Submariners live in an enclosed and isolated environment when at sea on a submerged submarine. Unlike workers who have respites from occupational exposures at the end of their shifts or workweeks, submariners are potentially exposed to air contaminants 24 hours (h) a day while the submarine is submerged. To protect submariners from 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 those contaminants.

EEGLs are defined as ceiling concentrations (concentrations not to be exceeded) of chemical substances in submarine air 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 lasting 1-24 h. Exposures at the EEGLs may induce reversible effects, such as ocular or upper respiratory tract irritation, and are therefore acceptable only in emergencies, when some discomfort must be endured. After 24 h of exposure, the CEGLs would apply. CEGLs are ceiling concentrations designed to prevent immediate or delayed adverse health effects or degradation in crew performance that might result from continuous exposures to chemical substances lasting up to 90 days.

In December 1995, the Navy began reviewing and updating the submarine exposure guidance levels. Because the National Research Council (NRC) Committee on Toxicology (COT) has previously reviewed and provided recommendations for those and other types of exposure guidance levels, the Navy requested that COT review, or develop when necessary, EEGLs and CEGLs for a variety of substances. As a result of the Navy’s request, the NRC convened the Subcommittee on Emergency and Continu-



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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants Summary Submariners live in an enclosed and isolated environment when at sea on a submerged submarine. Unlike workers who have respites from occupational exposures at the end of their shifts or workweeks, submariners are potentially exposed to air contaminants 24 hours (h) a day while the submarine is submerged. To protect submariners from 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 those contaminants. EEGLs are defined as ceiling concentrations (concentrations not to be exceeded) of chemical substances in submarine air 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 lasting 1-24 h. Exposures at the EEGLs may induce reversible effects, such as ocular or upper respiratory tract irritation, and are therefore acceptable only in emergencies, when some discomfort must be endured. After 24 h of exposure, the CEGLs would apply. CEGLs are ceiling concentrations designed to prevent immediate or delayed adverse health effects or degradation in crew performance that might result from continuous exposures to chemical substances lasting up to 90 days. In December 1995, the Navy began reviewing and updating the submarine exposure guidance levels. Because the National Research Council (NRC) Committee on Toxicology (COT) has previously reviewed and provided recommendations for those and other types of exposure guidance levels, the Navy requested that COT review, or develop when necessary, EEGLs and CEGLs for a variety of substances. As a result of the Navy’s request, the NRC convened the Subcommittee on Emergency and Continu-

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants ous Exposure Guidance Levels for Selected Submarine Contaminants in 2002. STATEMENT OF TASK Members of the COT subcommittee were selected for their expertise in inhalation toxicology, neurotoxicology, immunotoxicology, reproductive and developmental toxicology, veterinary pathology, pharmacokinetics, epidemiology, and human-health risk assessment. The subcommittee was specifically asked to accomplish the following tasks: Evaluate the Navy’s current and proposed 1-h and 24-h EEGLs and 90-day CEGLs for the following substances: 2190 oil mist, formaldehyde, acrolein, ozone, monoethanolamine, nitric oxide, nitrogen dioxide, oxygen, carbon dioxide, carbon monoxide, methanol, ammonia, benzene, hydrazine, Freon 12, Freon 114, hydrogen, toluene, and xylene. Determine whether the current or proposed guidance levels are consistent with the scientific data and whether any changes to the Navy’s exposure levels should be made on the basis of the subcommittee’s evaluation. For two submarine contaminants for which no guidance levels exist—surface lead and 2,6-di-t-butyl-4-nitrophenol—determine whether sufficient data are available to develop EEGLs and CEGLs, and if sufficient data are available, provide recommendations for guidance levels consistent with the data. Identify deficiencies in the database relevant to EEGL and CEGL development for the selected chemical substances, and make recommendations for future research, when appropriate. To accomplish its review, the subcommittee was asked to use the Navy’s supporting documentation and other relevant toxicologic and epidemiologic data and publish the results of its evaluations in two separate reports. This is the subcommittee’s first report. It contains the EEGL and CEGL recommendations for the following chemicals of concern to the Navy: acrolein, carbon dioxide, carbon monoxide, formaldehyde, hydrazine, methanol, monoethanolamine, nitric oxide, nitrogen dioxide, and oxygen. The remaining chemicals will be addressed in the second report.

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants APPROACH TO STUDY In conducting its evaluations, the subcommittee reviewed relevant human and animal data and used data selection criteria described in the NRC report Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.1 Where possible, primary references were used to derive the exposure guidance levels. Secondary references were used to support the estimates derived and the selection of critical end points. Whenever possible, studies that followed accepted standard scientific methods were selected as key studies (those used to derive the exposure guidance levels). Inhalation exposure studies were used to derive the EEGL and CEGL values. Data on other routes of exposure were considered where appropriate. Human studies were preferred over animal studies. When epidemiologic and human experimental studies were available, a preference typically was given to human experimental studies as these were conducted in a controlled laboratory setting and allowed measurement of personal exposure and end points relevant for derivation of the exposure guidance levels. When appropriate human data were not available, standard laboratory animal studies were used, with preference given to nonhuman primate studies. A weight-of-evidence approach was used to select key studies, thus ensuring that selected data were consistent with the overall scientific database and incorporated what is known about the biologic effects of a chemical on pertinent organ systems. For derivation of the EEGL and CEGL values, the subcommittee followed basic guidance provided by the NRC report Criteria and Methods for Preparing Emergency Exposure Guidance Level (EEGL), Short-term Public Emergency Guidance Level (SPEGL), and Continuous Exposure Guidance Level (CEGL) Documents,2 but also considered the guidance for 1 NRC (National Research Council). 2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals. Washington, DC: National Academy Press. 2 NRC (National Research Council). 1986. Criteria and Methods for Preparing Emergency Exposure Guidance Level (EEGL), Short-term Public Emergency Guidance Level (SPEGL), and Continuous Exposure Guidance Level (CEGL) Documents. Washington, DC: National Academy Press.

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants developing similar exposure levels provided in more recent NRC reports.3,4 The basis for the EEGLs was acute or short-term inhalation and ocular toxicity data, whereas the basis for the CEGLs was repeated inhalation exposure data, and the effects of cumulative exposures were considered. The most sensitive end points were emphasized for derivation of both exposure levels. Also, the subcommittee considered only those health end points relevant to healthy young adult men on the assumption that there are no women serving as permanent crew aboard submarines. When the key studies, health end points, and exposure levels were identified, the application of uncertainty factors was considered when extrapolating from animals to humans and when extrapolating from lowest-observed-adverse-effect levels to no-observed-adverse-effect levels. When necessary, other factors were applied to account for critical data gaps or for potentially relevant variations in susceptibilities. CONCLUSIONS AND RECOMMENDATIONS The subcommittee found substantial differences in the adequacy of the data sets used to derive the EEGLs and CEGLs. For example, formaldehyde has a robust data set that includes both occupational and controlled human studies, whereas monoethanolamine has a paucity of data available for determining effects following inhalation exposure. In fact, there are no human inhalation data for monoethanolamine, and the animal data available are considered incomplete because little information is provided about histologic, hematologic, and enzymatic changes that might occur following repeated or long-term exposure. Few chemicals have substantial data on long-term, low-level exposures. Specific recommendations for research needed to improve the confidence of the derived exposure levels are provided in the individual chemical profiles. In this report, the subcommittee makes recommendations for 1-h and 24-h EEGLs and 90-day CEGLs for the following chemicals: acrolein, carbon dioxide, carbon monoxide, formaldehyde, hydrazine, methanol, 3 NRC (National Research Council). 1992. Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants. Washington, DC: National Academy Press. 4 NRC (National Research Council). 2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals. Washington, DC: National Academy Press.

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants monoethanolamine, nitric oxide, nitrogen dioxide, and oxygen. Those recommendations are listed in Table S-1, and the Navy’s current and proposed values have been included in the table for comparative purposes. The bases for the subcommittee’s derivations are provided in the individual chemical profiles. Overall, the subcommittee considers the values proposed by the Navy for acrolein, carbon monoxide, formaldehyde, methanol, and nitrogen dioxide to be protective of submariners’ health. For carbon dioxide, hydrazine, and monoethanolamine, the subcommittee recommended 1-h EEGL values lower than those proposed by the Navy. The subcommittee considers the other guidance levels for those chemicals to be protective of submariners’ health. In the case of oxygen, the subcommittee recommended a higher minimal level for the 90-day CEGL than the one proposed by the Navy; the other minimal levels recommended by the subcommittee are lower than those the Navy has proposed. The subcommittee derived guidance levels for both nitric oxide and nitrogen dioxide, whereas the Navy proposed values for only nitrogen dioxide, assuming that those guidance levels would also be protective in the event of nitric oxide exposure. The subcommittee emphasizes that nitrogen dioxide must be monitored along with nitric oxide, because nitric oxide can combine with oxygen to form nitrogen dioxide, which is more toxic than nitric oxide. RESEARCH RECOMMENDATIONS The submarine atmosphere does not appear to be well characterized. In conducting its evaluation, the subcommittee found that few exposure data are available on the Navy’s chemicals of concern or other chemicals. This subcommittee agrees with a previous NRC report, Submarine Air Quality5 and recommends again that “the Navy thoroughly survey various classes of submarines for trace contaminants and particulate matter” and that “monitoring on submarines provide complete analysis of submarine air and data on exposure of personnel to contaminants.” Furthermore, if the exposure assessments indicate that certain chemicals pose problems (that is, concentrations are higher than 90-day CEGLs), relative source contribu- 5 NRC (National Research Council). 1988. Submarine Air Quality: Monitoring the Air in Submarines. Washington, DC: National Academy Press.

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants TABLE S-1 Comparison of Navy’s Exposure Guidelines with Those Recommended by the Subcommittee Chemical Exposure Level U.S. Navy Valuesa NRC Recommended Valuea Current Proposed Acrolein 1-h EEGL 0.05 0.07 0.1   24-h EEGL 0.01 0.03 0.1   90-day CEGL 0.01 0.01 0.02 Carbon dioxide 1-h EEGL 40,000 30,000 25,000   24-h EEGL 40,000 15,000 25,000   90-day CEGL 5,000 7,000 8,000 Carbon monoxide 1-h EEGL 400 55 180   24-h EEGL 50 20 45   90-day CEGL 20 10 9 Formaldehyde 1-h EEGL 3 0.4 2   24-h EEGL 1 0.1 1   90-day CEGL 0.5 0.04 0.3 Hydrazine 1-h EEGL — 4 1   24-h EEGL — 0.3 1   90-day CEGL — 0.01 0.03 Methanol 1-h EEGL 200 200 600   24-h EEGL 10 10 50   90-day CEGL 10 7 10 Monoethanolamine 1-h EEGL 50 6 4   24-h EEGL 3 3 4   90-day CEGL 0.5 0.5 0.5 Nitric oxideb 1-h EEGL — — 130   24-h EEGL — — 50   90-day CEGL — — 3 Nitrogen dioxide 1-h EEGL 1 3 10   24-h EEGL 1 1 2   90-day CEGL 0.5 0.5 0.7 Oxygen (min.-max.) 1-h EEGL 130-220 mmHg — 105 mmHg (min.)   24-h EEGL 130-160 mmHg — 127 mmHg (min.)   90-day CEGL 130-160 mmHg — 140 mmHg (min.) aAll values in parts per million (ppm) unless otherwise noted. bNavy considers the guidance levels for nitrogen dioxide to be also protective of nitric oxide exposure. Abbreviations: max., maximum; min., minimum; mmHg, millimeters of mercury.

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Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants tions should be determined for those chemicals. The subcommittee notes that a few onboard sources, such as cigarette smoking and certain cooking methods, contribute to the formation of multiple compounds considered in this report. Therefore, stricter management or elimination of those sources is likely to solve some exposure problems on board submarines. The subcommittee did not address exposures to chemical mixtures. When empirical data that characterize mixtures found in submarine air become available, the subcommittee recommends that they be evaluated. The potential for antagonistic, additive, or synergistic interactions between contaminants in the submarine environment is an area of significant uncertainty that remains largely unexamined and needs to be studied. Several of the chemicals that the subcommittee evaluated for this report are sensory irritants. The derivation of quantitative environmental and occupational exposure limits for sensory irritants is fraught with difficulty because measures of the ocular and respiratory tract irritation experienced by human subjects are often considered subjective. The results of controlled human exposures to many sensory irritants typically use descriptors, such as “mild” or “mild to moderate,” and the database for sensory irritation thresholds can be highly variable. Research is needed to quantify the diverse methods and end points used in sensory irritation studies, so that these data can be used in public- and occupational-health risk assessment with greater confidence.