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Toxicologic Assessment of Jet-Propulsion Fuel 8 (2003)

Chapter: Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)

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Suggested Citation:"Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
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Page 162
Suggested Citation:"Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
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Page 163
Suggested Citation:"Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
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Page 164
Suggested Citation:"Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
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Page 165
Suggested Citation:"Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
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Page 166
Suggested Citation:"Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 167
Suggested Citation:"Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 168
Suggested Citation:"Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 169
Suggested Citation:"Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 170
Suggested Citation:"Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 171
Suggested Citation:"Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
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Page 172

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Appendix A Permissible Exposure Levels for Selected Military Fuel Vapors: Contents and Executive Summary (NRC 1996)

Permissible Exposure Levels for Selected Military Fuel Vapors SUBCOMMITTEE ON PERMISSIBLE EXPOSURE LEVELS FOR MILITARY FUELS COMMITTEE ON TOXICOLOGY BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY COMMISSION ON LIFE SCIENCES NATIONAL RESEARCH COUNCIL NATION AL ACAD EMY PRESS WASH INGTO N, D.C., 1996

Contents E XECUTIVE S UMMARY 1 1 I NTRODUCTION 9 2 P HYSICAL AND C HEMICAL P ROPERTIES OF M ILITARY F UELS 13 Jet-Propulsion Fuel 5 15 Jet-Propulsion Fuel 8 16 Diesel Fuel Marine 17 3 T OXICOKINETICS OF M ILITARY F UELS 18 General Determ inants of Hydrocarbon Toxicokinetics 19 Toxicokinetics of Specific Military Fuel Hydrocarbons 22 Simulated Tissue Concentrations After Exposure to Com ponents of M ilitary Fuels 27 4 FUEL EXPOSURES, TOXICITY TESTING, AND AIR MONITORING IN N AVAL O PERATION S 36 Vapor Composition 37 Setting PELs for Mixtures 39 Implications for Toxicity Testing 40 Implications for Air Monitoring 40 164

Appendix A 165 5 E FFECTS OF M ILITARY F UEL V APORS ON THE K IDNEY 44 Effects of Acute E xposures to Fuel Vapors 44 Effects of Subchronic Exposures to Fuel Vapors 45 Conclusions 49 6 E FFECTS OF M ILITARY F UEL V APORS ON THE H EMATOPOIETIC S YSTEM 51 Hem atological Effects of JP-5 Fuel Vapors 51 Hem atological Effects of JP-8 Fuel Vapors 53 Hem atological Effects of DF M Fuel Vapors 54 Conclusions 55 7 EFFECTS OF MILITARY FUEL VAPORS ON THE C ENTRAL N ERVOU S S YSTEM 56 Neurophysiological and Psychological Effects of Fuel Vapors 57 Relationship between STEL and Minim um Alveolar Concentrations 65 Conclusions 66 8 E FFECTS OF M ILITARY F UEL V APORS ON THE L IVER 69 Hepatic Effects of JP-5 Fuel Vapors 69 Hepatic Effects of JP-8 Fuel Vapors 72 Hepatic Effects of DFM Fuel Vapors 73 Hepatic Effects of JP-4 Fuel Vapors 75 Conclusions 77 9 E FFECTS OF M ILITARY F UEL V APORS ON THE C ARDIOVASCULAR S YSTEM 82 10 C ARC INO GEN IC E FFECTS OF M ILITARY F UEL V APORS 84 Epidemiological Studies 84 Experimental Animal Studies 96 Conclusions 100 11 G ENO TOX IC E FFECTS OF M ILITARY F UEL V APORS 101 Assay Testing for Genotoxicity 101 Conclusions 103 12 E FFECTS OF M ILITARY F UELS ON THE E YES AND S KIN 104 Dermal and Ocular E ffects of JP-4 Fuel 104 Dermal and Ocular E ffects of Diesel Fuel 105

166 Appendix A Dermal and Ocular Effects of JP-8 Fuel 106 Dermal and Ocular E ffects of DFM Fuel 107 Dermal and Ocular E ffects of JP-5 Fuel 107 Conclusions 108 13 C ONCLUSIONS AND R ECOMMENDATIONS 109 R EFERENCES 112 A PPEN DIX A. Program : Model for Two V olatile Organics 123

Executive Summary The U.S. Navy is in the final stages of designing a strategic sealift ship to transport already-fueled vehicles—armored tanks, tanker trucks, other trucks of various sizes, trailers, jeeps, and helicopters. Prefueling will eliminate the need for fueling at docking and will permit deployment of the vehicles as soon as they are unloaded from the ship. All the military vehicles transported on the ship are designed to use jet-propulsion (JP) fuels JP-5 or JP-8 to avoid the need for different fuels. Diesel fuel marine (DFM ) is used to operate the ship. The Navy’s Occupational Safety and Health Standards Board has consid- ered the potential for storage and operation of the fueled vehicles in the ship’s cargo holds to be hazardous to naval service personnel exposed to fuel vapors during the servicing of these vehicles or while working in their vicinity. To protect personnel from exposures to toxic concentrations of fuel vapors, the board recommended an interim 8-hr time-weighted average (TWA) perm issi- ble exposure limit (PEL) of 350 mg/m 3 and a 15-m in short-term exposure limit (STEL) of 1,800 mg/m 3 for vapors from all three fuels. Those interim exposure limits were based on the board’s review of the manufacturers’ tech- nical documentation and the National Institute of Occupational Safety and Health’s recommendations for maximum exposure to refined petroleum solvents. The Navy decided that an independent review of the proposed interim exposure limits would be useful and requested that the National Research Council (NRC) perform the following tasks: (1) review the toxicity data on 167

168 Appendix A these fuels, (2) determine the adequacy of the Navy’s proposed PELs and STE Ls, and (3) recom mend changes, if needed, to the proposed limits. In response to the Navy’s request, the NRC assigned this project to the Committee on Toxicology (COT). The COT convened the Subcommittee on Perm issible Exposu re Levels for Military Fuels, 1 which prepared this report. The subcom mittee based its evaluation of the Navy’s interim PELs and STELs on a detailed examination of current data on the toxicity of fuel vapors from JP-5, JP-8, JP-4, and DFM in anim als and humans. JP-4 is included in this analysis because more information is available on the toxicity of JP-4 vapors than on the other three fuels and because the composition of JP-4 vapors is sufficiently sim ilar to those of JP-5 and JP-8 vapors. The toxicity of the vapors from all these fuels is expected to be similar. The subcom mittee did not address the potential toxicity resulting from exposure to respirable aerosols of the total fuels. If the Navy finds evidence of potential for exposures to respirable aerosols, which are much more toxic, new recommendations for limiting such exposures will need to be developed. It is understood that the board intends to use the exposure levels for the three fuels to help determine ventilation requirements in the cargo holds of the new strategic sealift ships and to prevent toxic exposures of service personnel to these fuels. ADVERSE EFFECTS The m ajor adverse effects resulting from inhalation of these military fuel vapors are kidney, central-nervous-system (CN S), liver, and carcinogenic effects. Kidney The renal toxicity of these military fuels was studied in rats and mice of both sexes. Adverse effects in the kidneys were observed only in male rats after inhalation exposure. Histological sections from the kidneys of affected anim als were examined, and the presence of the characteristic hyaline droplets, suggestive of an "2u-globulin pathogenesis, was confirmed. Current scientific thinking is that these findings are not relevant to humans because this kidney lesion appears to be unique to the male rat. 1 The term “military fuels” in this report refers only to JP-5, JP-8, JP-4, and DFM vapors.

Appendix A 169 Central Nervous System In one epidem iological investigation, 30 workers exposed to jet fuel at a Swedish jet-motor factory for an average of 17 years were studied for possible adverse health effects. The TWA exposure concentrations from one-time measurements of workers in different job categories were calculated to be 420 mg/m 3 for component testers, 130 mg/m 3 for engine testers, and 190-250 mg/m 3 for mechanics. The overall TWA concentration from one-time mea- surements was 300 mg/m 3; peak exposures ranged from approximately 1,200 to 3,200 mg/m 3. Significant differences between the exposed and nonexposed workers were found with respect to CNS effects. The majority of the exposed workers reported acute sym ptoms of dizziness, headache, nausea, and fatigue. Chronic symptoms included greater incidence of neurasthenic symptoms (depressed mood, lack of initiative, sleep disturbances, mem ory impairment, headache, dizziness, and fatigue). The exposed workers also showed higher performance degradation in a variety of performance tests than the nonexposed workers. The neurophysiological examination with electroenceph- alograms showed greater incidence of abnormalities in jet-fuel exposed work- ers than in nonexposed workers. However, the findings of CNS effects attrib- utable to long-term exposure were considered questionable for a number of reasons, including weak and inconsistent evidence of impairment, inadequate methods of evaluation, inadequate consid eration of confound ing factors, a small cohort of workers,and a lack of quantitative information on exposure. Liver Several investigators have studied the effects of subchronic exposure to military fuel vapors on the liver in experimental animals. No liver histopatho- logical changes were found in three inhalation studies in which anim als were exposed intermittently (occupational-type exposure) to fuel vapors. In one study, rats exposed to JP-5 vapors at concentrations of 1,000 or 1,600 mg/m 3 for 6 hr per day, 5 days per week for 6 weeks showed no evidence of adverse effects on the liv er. In the second study, rats, mice, dogs, and monkeys ex- posed to JP-4 vapors at 2,500 or 5,000 mg/m 3 for 6 hr per day, 5 days per week for 8 months showed no evidence of exposure-related effects except a slight increase in liver weight in the female rats. In the third study, rats and mice exposed to JP-4 vapors at 1,000 or 5,000 mg/m 3 for 6 hr per day, 5 days per week for 12 months show ed no liver toxicity. N o clear evidence of hepatic neoplasia in rats or mice was found. Based on this study, the subcommittee identified a no-observed-adverse-effect level (NOA EL) of 5,000 mg/m 3,

170 Appendix A which was used to calculate the PEL. By dividing the NO AE L of 5,000 mg/m 3 by an uncertainty factor of 10 for interspecies extrapolation, the PEL was calculated to be 500 mg/m 3. No uncertainty factor for intraspecies varia- tion was applied because the exposed Navy personnel are considered to be healthy. Carcinogenicity Carcinogenicity of military fuels has been studied in humans and animals. An epidemiological study of approxim ately 2,200 Swedish military personnel exposed to jet-fuel vapors at concentrations greater than 350 mg/m 3 for sev- eral years did not show increased incidence of cancer. It should be noted that this study was only capable of detecting high risks of cancer because there were few cancer deaths, the sam ple was small, and the follow up was short. Several studies of petroleum workers, ranging from refinery workers to service-station attendants, reported increases in cancer, but few studies re- ported on persons exposed only to jet-fuel vapors. Exposure to benzene appears to be of consequence in many of the excesses found. In long-term animal studies involving inhalation exposure to unleaded gasoline, kidney cancers were observed only in male rats. That finding raises the question of whether longer exposure of male rats to JP-5, JP-8, or DFM might also result in increased kidney cancers. However, the increased incidence of kidney can- cer in male rats exposed to the gasoline was due to an "2u-globulin nephropathy—a lesion that apparently does not occur in humans, in other animals, or in female rats. Based on the available human and animal data, the subcommittee con- cluded that inhalation of JP-5, JP-8, and DFM vapors does not present a carcinogenic risk to humans. That conclusion is supported by studies that show that these military fuels are not genotoxic. However, laboratory studies provided evidence of potential carcinogenicity of DFM via the dermal route. Epidemiological studies show skin-cancer excesses in certain industrial work- ers, such as machine operators, whose skin might com e into contact with lubricating oils derived from coal tar or petroleum. Exposure conditions in the studies that resulted in excessive skin damage are unlikely to occur on Navy ships. CONCLUSIONS AND RECOMMENDATIONS The Am erican Conference of Governm ental Industrial Hygienists has not recommended exposure limits for the military fuels that are the subject of this

Appendix A 171 report. The O ccupational Safety and Health Administration and other regula- tory agencies also have not promulgated standards for these fuels. The toxicity data on military fuels are sparse. No reliable information was found to indicate a need to change the Navy’s proposed PEL of 350 mg/m 3. The findings in Swedish jet-motor factory workers of chronic CNS effects—performance degradation and neurasthenic symptoms—attributable to long-term exposure to jet fuels at TWA concentrations of 300 mg/m 3 were considered questionable for reasons discussed above. The studies of hepatotoxicity in experimental animals were also considered to be of question- able significance. The PEL of 500 mg/m 3 was based on a slight increase in liver weight in rats—an effect that was reversible and not accompanied by any histopathological change. Based on the available information from studies in humans and animals and based on expert judgment, the subcommittee con- cludes that the Navy board’s 8-hr PE L of 350 mg/m 3 for JP-5, JP-8, and DFM is adequate to protect the health of naval personnel occupationally exposed to military fuels. Due to the uncertainty surrounding (1) the CNS effects observed in Swedish jet-m otor factory workers from chronic exposure to jet fuel at TWA concentrations of 300 mg/m 3 and (2) the NOAE L of 500 mg/m 3 derived from liver toxicity studies in rats and mice, the subcommittee recommends that the PEL of 350 mg/m 3 be considered interim until further research is completed. Data needed to evaluate the adequacy of the Navy’s 15-min STEL of 1,800 mg/m 3 for the three fuels are sparse. The subcommittee considered the acute CNS effects (e.g., dizziness, headache, nausea, and fatigue) in the Swed- ish jet-motor factory workers to be the most critical health effects for deter- mining the adequacy of the STELs. Based on the limited information on exposure concentrations and the attribution of CNS symptoms to peak expo- sures of approximately 1,000 mg/m 3 or higher, the subcommittee recom- mends that the Navy’s current STEL be lowered from 1,800 mg/m 3 to 1,000 mg/m 3 to avoid acute CNS toxicity. The STEL of 1,000 mg/m 3 should also be considered an interim recomm endation until further research is completed. The subcommittee also recommends the following: • Appropriate protective clothing should be worn to reduce dermal exposure because of the evidence of the carcinogenic pote ntial of DFM via the dermal route. • Because respirable aerosols of military fuels are much m ore toxic than vapors, naval personnel should avoid exposure to aerosolized fuel. If a poten- tial for exposure to aerosolized fuel exists, protective clothing and respiratory equipment should be worn. • The Navy should com plete the following research to improve its ability to assess the health risks associated with the use of military fuels:

172 Appendix A —Obtain information on exposures occurring during operational procedures, including exposures to respirable aerosols of unburned fuels. Samples should be talon in the breathing zone of the service personnel. Breath analysis of exposed personnel is recomm ended to determine the extent of individual exposures to fuel vapors. —Conduct studies on the possible effects of high-level acute and low- level chronic exposure to m ilitary fuel vapors on the CN S, including the ef- fects on the performance of personnel. At present, very little information exists. Anecdotal accounts do not provide adequate documentation of expo- sures leading to reduced performance. —C onduct further research on the effect of military fuel vapors on hepatotoxicity in experimental anim als; this research would help to identify the NO AEL with greater confidence.

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This report provides a critical review of toxicologic, epidemiologic, and other relevant data on jet-propulsion fuel 8, a type of fuel in wide use by the U.S. Department of Defense (DOD), and an evaluation of the scientific basis of DOD's interim permissible exposure level of 350 mg/m3

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