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



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

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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 NATIONAL ACADEMY PRESS WASHINGTON, D.C., 1996

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Contents     EXECUTIVE SUMMARY   1     1 INTRODUCTION   9     2 PHYSICAL AND CHEMICAL PROPERTIES OF MILITARY FUELS   13     Jet-Propulsion Fuel 5   15     Jet-Propulsion Fuel 8   16     Diesel Fuel Marine   17     3 TOXICOKINETICS OF MILITARY FUELS   18     General Determinants of Hydrocarbon Toxicokinetics   19     Toxicokinetics of Specific Military Fuel Hydrocarbons   22     Simulated Tissue Concentrations After Exposure to Components of Military Fuels   27     4 FUEL EXPOSURES, TOXICITY TESTING, AND AIR MONITORING IN NAVAL OPERATIONS   36     Vapor Composition   37     Setting PELs for Mixtures   39     Implications for Toxicity Testing   40     Implications for Air Monitoring   40

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    5 EFFECTS OF MILITARY FUEL VAPORS ON THE KIDNEY   44     Effects of Acute Exposures to Fuel Vapors   44     Effects of Subchronic Exposures to Fuel Vapors   45     Conclusions   49     6 EFFECTS OF MILITARY FUEL VAPORS ON THE HEMATOPOIETIC SYSTEM   51     Hematological Effects of JP-5 Fuel Vapors   51     Hematological Effects of JP-8 Fuel Vapors   53     Hematological Effects of DFM Fuel Vapors   54     Conclusions   55     7 EFFECTS OF MILITARY FUEL VAPORS ON THE CENTRAL NERVOUS SYSTEM   56     Neurophysiological and Psychological Effects of Fuel Vapors   57     Relationship between STEL and Minimum Alveolar Concentrations   65     Conclusions   66     8 EFFECTS OF MILITARY FUEL VAPORS ON THE LIVER   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 EFFECTS OF MILITARY FUEL VAPORS ON THE CARDIOVASCULAR SYSTEM   82     10 CARCINOGENIC EFFECTS OF MILITARY FUEL VAPORS   84     Epidemiological Studies   84     Experimental Animal Studies   96     Conclusions   100     11 GENOTOXIC EFFECTS OF MILITARY FUEL VAPORS   101     Assay Testing for Genotoxicity   101     Conclusions   103     12 EFFECTS OF MILITARY FUELS ON THE EYES AND SKIN   104     Dermal and Ocular Effects of JP-4 Fuel   104     Dermal and Ocular Effects of Diesel Fuel   105

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    Dermal and Ocular Effects of JP-8 Fuel   106     Dermal and Ocular Effects of DFM Fuel   107     Dermal and Ocular Effects of JP-5 Fuel   107     Conclusions   108     13 CONCLUSIONS AND RECOMMENDATIONS   109     REFERENCES   112     APPENDIX A. Program: Model for Two Volatile Organics   123

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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 considered 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) permissible exposure limit (PEL) of 350 mg/m3 and a 15-min short-term exposure limit (STEL) of 1,800 mg/m3 for vapors from all three fuels. Those interim exposure limits were based on the board’s review of the manufacturers’ technical 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

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these fuels, (2) determine the adequacy of the Navy’s proposed PELs and STELs, and (3) recommend 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 Permissible Exposure Levels for Military Fuels,1 which prepared this report. The subcommittee 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 animals 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 similar to those of JP-5 and JP-8 vapors. The toxicity of the vapors from all these fuels is expected to be similar. The subcommittee 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 major adverse effects resulting from inhalation of these military fuel vapors are kidney, central-nervous-system (CNS), 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 animals were examined, and the presence of the characteristic hyaline droplets, suggestive of an α2u-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.

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Central Nervous System In one epidemiological 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/m3 for component testers, 130 mg/m3 for engine testers, and 190-250 mg/m3 for mechanics. The overall TWA concentration from one-time measurements was 300 mg/m3; peak exposures ranged from approximately 1,200 to 3,200 mg/m3. Significant differences between the exposed and nonexposed workers were found with respect to CNS effects. The majority of the exposed workers reported acute symptoms of dizziness, headache, nausea, and fatigue. Chronic symptoms included greater incidence of neurasthenic symptoms (depressed mood, lack of initiative, sleep disturbances, memory 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 workers than in nonexposed workers. However, the findings of CNS effects attributable to long-term exposure were considered questionable for a number of reasons, including weak and inconsistent evidence of impairment, inadequate methods of evaluation, inadequate consideration of confounding 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 histopathological changes were found in three inhalation studies in which animals 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/m3 for 6 hr per day, 5 days per week for 6 weeks showed no evidence of adverse effects on the liver. In the second study, rats, mice, dogs, and monkeys exposed to JP-4 vapors at 2,500 or 5,000 mg/m3 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/m3 for 6 hr per day, 5 days per week for 12 months showed no liver toxicity. No clear evidence of hepatic neoplasia in rats or mice was found. Based on this study, the subcommittee identified a no-observed-adverse-effect level (NOAEL) of 5,000 mg/m3,

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which was used to calculate the PEL. By dividing the NOAEL of 5,000 mg/m3 by an uncertainty factor of 10 for interspecies extrapolation, the PEL was calculated to be 500 mg/m3. No uncertainty factor for intraspecies variation 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 approximately 2,200 Swedish military personnel exposed to jet-fuel vapors at concentrations greater than 350 mg/m3 for several 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 sample 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 reported 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 cancer in male rats exposed to the gasoline was due to an α2u-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 concluded 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 workers, such as machine operators, whose skin might come 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 American Conference of Governmental Industrial Hygienists has not recommended exposure limits for the military fuels that are the subject of this

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report. The Occupational Safety and Health Administration and other regulatory 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/m3. 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/m3 were considered questionable for reasons discussed above. The studies of hepatotoxicity in experimental animals were also considered to be of questionable significance. The PEL of 500 mg/m3 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 concludes that the Navy board’s 8-hr PEL of 350 mg/m3 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-motor factory workers from chronic exposure to jet fuel at TWA concentrations of 300 mg/m3 and (2) the NOAEL of 500 mg/m3 derived from liver toxicity studies in rats and mice, the subcommittee recommends that the PEL of 350 mg/m3 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/m3 for the three fuels are sparse. The subcommittee considered the acute CNS effects (e.g., dizziness, headache, nausea, and fatigue) in the Swedish jet-motor factory workers to be the most critical health effects for determining the adequacy of the STELs. Based on the limited information on exposure concentrations and the attribution of CNS symptoms to peak exposures of approximately 1,000 mg/m3 or higher, the subcommittee recommends that the Navy’s current STEL be lowered from 1,800 mg/m3 to 1,000 mg/m3 to avoid acute CNS toxicity. The STEL of 1,000 mg/m3 should also be considered an interim recommendation 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 potential of DFM via the dermal route. Because respirable aerosols of military fuels are much more toxic than vapors, naval personnel should avoid exposure to aerosolized fuel. If a potential for exposure to aerosolized fuel exists, protective clothing and respiratory equipment should be worn. The Navy should complete the following research to improve its ability to assess the health risks associated with the use of military fuels:

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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 recommended 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 military fuel vapors on the CNS, including the effects on the performance of personnel. At present, very little information exists. Anecdotal accounts do not provide adequate documentation of exposures leading to reduced performance. Conduct further research on the effect of military fuel vapors on hepatotoxicity in experimental animals; this research would help to identify the NOAEL with greater confidence.