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Toxicologic Assessment of Jet-Propulsion Fuel 8 (2003)

Chapter: 2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8

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Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." 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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Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." 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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Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." 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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Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." 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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Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." 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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Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 21
Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 22
Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 23
Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 24
Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 25
Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 26
Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." National Research Council. 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. doi: 10.17226/10578.
×
Page 27
Suggested Citation:"2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8." 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 28

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2 Dosimetry and Exposure Assessment of Jet-Propulsion Fuel 8 This chapter discusses issues relevant to assessing exposure of military person- nel to jet-propulsion fuel 8 (JP-8). The chapter begins with a description of various scenarios under which military personnel are exposed to JP-8, fol- lowed by a brief discussion of the challenges of quantifying human exposure to this distillate fuel. The next section contains a summary of data from stud- ies that have measured concentrations of several components of JP-8 in ambi- ent air at Air Force aircraft maintenance sites. Studies measuring body burden of several JP-8 components in workers involved in aircraft maintenance are also presented. The final section of this chapter describes how the physical and chemical properties of JP-8 affect uptake into the body from exposure by the inhalation, dermal, and oral routes. This last section also serves as a pre- lude to interpretation of animal toxicity studies conducted with distillate fuels (e.g., JP-8) that are described in later chapters. BACKGROUND Henz (1998) recently estimated that the U.S. Department of Defense (DOD) and North Atlantic Treaty Organization (NATO) partners use 5 bil- 16

Dosimetry and Ex posure A ssessment of Jet-Propulsion F uel 8 17 lion gallons of JP-8 per year for powering aircraft and land-based military vehicles. Quantitatively and qualitatively, JP-8 is probably responsible for the most common and abundant potential chemical exposure of DOD and NATO personnel. Occupational exposure of military and civilian personnel to JP-8 may occur in the following settings (see Table 2-1): transportation and storage of JP-8 fuel; aircraft fueling and defueling; maintenance of aircrafts; cold engine starts and performance testing; and operation and maintenance of other Air Force equipment and machinery. Air Force personnel working in aircraft fuel-cell maintenance shops and fuels-specialty and fuels-transporta- tion shops are probably at the greatest risk for exposure to JP-8 (ATSDR 1998; R. Gibson, U.S. Air Force, personal communication, 2001). Additional exposure scenarios include application of JP-8 in fueling military tent heaters, use of fuel as an aircraft heat sink, and cleaning and degreasing with fuel (CDC 1999; Zhou and Cheng 2000; Cheng et al. 2001). During the Persian Gulf War, JP-8 was routinely used to control and suppress desert sand, and combusted JP-8 fuel was used to obscure troops and equipment (CDC 1999). With desert surface temperatures commonly exceeding 120°F, substantial exposure may have occurred as a result of vaporization of JP-8. When vapor- ized jet fuel mixes with wind-blown ultrafine desert sand particles, pulmonary exposure is highly possible. ASSESSMENT OF OCCUPATIONAL EXPOSURE TO JP-8 Deliberations on the scientific basis of the interim permissible exposure level (PEL) of 350 mg/m3 for JP-8 required the subcommittee to review relevant exposure assessment, epidemiologic, and toxicologic data. The stud- ies all involved exposure to JP-8 or similar compounds; however, in many studies it is a challenge to qualitatively and quantitatively assess the exposure and dose of components of JP-8. Measurement of occupational exposures in various settings is problematic because JP-8 is a complex mixture of chemicals and personnel may be exposed to vapors, aerosols, or both, depending on the workplace setting. Furthermore, there are no standardized industrial hygiene sampling methods or analytical methods for JP-8. Ambient concentrations have been measured with standard industrial-hygiene methods to quantify some components of JP-8 (mostly aromatic substances, including benzene, naphthalene, toluene, and xylene). Given that the major chemical constituents of JP-8 are C9-C17+ aliphatic hydrocarbons, it is unclear how these aromatic components represent a true measure of total occupational exposure to JP-8.

18 Toxicologic A ssessment of Jet-Propulsion F uel 8 TABLE 2-1 Major JP-8 Exposure Scenarios Exposu re Scenario DO D Personnel Exposure Type Cold starts Ground crew Aerosol, vapor, liqu id Fueling, defueling Fuelers Aerosol, vapor, liqu id Engine, fuel cells Maintena nce wo rkers Vapor, liquid Repair Maintena nce wo rkers Vapor, liquid Fuel transport Fuel handlers Aerosol, vapor, liqu id Stoves, heaters General troops Vapor, liquid Spills Cleanup crews Vapor, liquid Tanks, ground vehicles General troops Vapor, liquid Sou rce: Witte n 2002. R eprinted with permission of the author. JP-8 Concentrations in Ambient Air Pleil et al. (2000) reported on the collection of area breathing-zone samples taken at fuel maintenance operation sites at a number of domestic Air Force bases with commercially available, compact, battery-operated, personal whole-air samplers. The ambient air concentrations were 2,987 parts per billion (ppb) for benzene, 16,026 ppb for toluene, 9,588 ppb for ethylbenzene, 20,993 ppb for xylenes, 34,138 ppb for nonane, 31,344 ppb for decane, and 31,007 ppb for undecane (Pleil et al. 2000). Carlton and Smith (2000) mea- sured JP-8 (based on total hydrocarbons) and benzene vapor concentrations during aircraft fuel-tank entry and repair at 12 Air Force bases. The highest 8-hr time-weighed average (TWA) fuel exposure was 1,304 mg/m3; the highest 15-min short-term exposure was 10,295 mg/m3. Overall, workers who re- paired fuel tanks that contained explosion-suppression foam had the highest exposure to JP-8 total hydrocarbons compared with workers who repaired fuel tanks without foam. The highest benzene exposure in workers involved in the repair of foamed fuel tanks was 49.1 :g/m3. Fuel tanks with cross ventilation had much lower concentrations of JP-8 than fuel tanks with poor ventilation. In an Australian study, JP-8 vapor concentrations were found to reach 2,823 mg/m3 inside wet B747 aircraft fuel tanks (Yeung et al. 1997). Recently, the Air Force assessed the potential health effects of acute expo- sure to JP-8 (TIEHH 2001; see Appendix B). The subjects were selected from several Air Force bases and placed in two groups: workers who were routinely exposed to JP-8 as part of their Air Force Specialty Code (workers involved in maintenance of aircraft-fuel cells were considered highly exposed and work- ers employed in fuels-transportation shops were considered moderately ex-

Dosimetry and Ex posure A ssessment of Jet-Propulsion F uel 8 19 posed) and age- and sex-matched unexposed referents (Air Force active-duty personnel with no direct contact with JP-8). JP-8 exposed workers entering aircraft-fuel cells wore respirators and coveralls, which are permeable and absorbent, so there was an opportunity for substantial dermal exposure to JP- 8. Preliminary results indicate that the median concentration of naphthalene in air measured in the breathing zone of subjects in the low-exposure category (workers with no routine contact with JP-8) was 1.9 :g/m3, about 4 times the concentration in ambient air (Egeghy and Rappaport 2001). The median benzene concentration was 3.1 :g/m3 (2-fold less than global outdoor benzene concentration). In the moderate-exposure group, the median naphthalene and benzene concentrations were 10.4 and 7.45 :g/m3, respectively. In the high- exposure group, the concentrations of those chemicals were at least 30 times higher than for the moderate-exposure group. Overall, JP-8 air concentrations according to surrogate markers, such as total hydrocarbons, naphthalene, and benzene, appeared to be highest in aircraft fuel tanks, especially those containing explosion-suppression foam (Carlton and Smith 2000; Egeghy and Rappaport 2001). The increased air concentrations appear to result from the tendency of foam to absorb fuel. At elevated temperatures inside the tank, the fuel volatilizes to yield higher air concentrations of JP-8. Fuel tanks with appropriate cross ventilation have much lower interior air concentrations of JP-8. Estimates of Dermal Exposure Skin can be an important route of JP-8 exposure. Aircraft fuel-mainte- nance workers may be exposed to liquid jet fuel for more than 10 min, which gives ample opportunity for dermal exposure. Except for chemical-resistant eyewear, footwear, gloves, and cotton coverall jumpsuits, which are permeable to JP-8, there is little protection of skin. Prolonged JP-8 skin contact can induce irritation, contact dermatitis, and sensitization (Wolfe et al. 1997; Ullrich 1999). Nylander-French and Archer (2001) reported preliminary results of an acute dermal-exposure study conducted with Air Force fuel-cell maintenance workers. A noninvasive tape-stripping technique was used to measure JP-8 concentrations in skin using naphthalene as a surrogate marker of exposure to the whole fuel. The technique permits the estimation of the dermal reten- tion of JP-8 after the removal of stratum corneum by successive tape stripping with an adhesive tape. The high-exposure group (workers involved in mainte- nance of aircraft-fuel cells) had the highest skin exposure but also had the highest variability (5 orders of magnitude). Compared with the high-exposure

20 Toxicologic A ssessment of Jet-Propulsion F uel 8 group, exposure in the moderate- and low-dose groups (workers employed in fuels-transportation shops and unexposed referents, respectively) followed a descending trend. The mean, median, and range of naphthalene exposure for all subjects were 35.7, 15.0, and less than the limit of detection to 25,287 ng per tape strip, respectively. That mean naphthalene mass did not change substantially between various strippings suggests that naphthalene was able to penetrate the stratum corneum. Such penetration can contribute to delayed and cumulative systemic absorption of some JP-8 components through skin. Given that over 200 hydrocarbons are present in JP-8 and that hydrocarbons differ in skin disposition, overall skin absorption of JP-8 components remains poorly characterized. The use of surrogate markers representing a few hydro- carbons is at most a qualitative assessment of dermal exposure to JP-8 fuels. MEASUREMENT OF BODY BURDEN OF JP-8 Environmental monitoring of JP-8 is crude and can lead to incorrect information about body burdens of JP-8 constituents. In a recent preliminary Air Force acute-exposure study, JP-8 components were measured in blood in a highly exposed group (fuel-cell maintenance workers) and an unexposed referent group (Gibson et al. 2001). The surrogate exposure to JP-8 was assessed as a “JP-8 fingerprint” representing the combined concentration of various aliphatic hydrocarbons, including nonane, decane, undecane, and dodecane. The JP-8 fingerprint index represents 15% of the JP-8 vapor and 11% of the liquid vapor. In the high-exposure group of workers, the concen- tration range was extremely large with values ranging from 1 to 124 ng/mL (mean, 10.24 ng/mL; median, 6 ng/mL). In the referent group, the concen- tration in the JP-8 fingerprint was 0-45 ng/mL (mean, 2.15 ng/mL; median, near zero). In addition to interperson and intergroup variability, there was a large variability in exposure among workers at various Air Force bases. That could reflect differences in exposure and variation in fuel contents. Other factors affecting variability include the amount of lipid in blood, hemoglobin concentration, meal patterns, and body fat. Pleil (2001) analyzed preexposure and postexposure breath samples for a number of single-ring hydrocarbons (such as benzene, toluene, ethylbenzene, m-xylene, 4-ethyltoluene, 1,3,5-trimethylbenzene, and styrene) and C9-C12 n- alkanes and identified them collectively as a JP-8 fingerprint. The JP-8 expo- sure measurement in expired air was considered an important indicator of aggregate exposure and may collectively represent the transient JP-8 body burden from inhalation and dermal exposure. As indicated earlier, there was a large variation among bases in exposure to JP-8. Preliminary results show that at one Air Force base in Little Rock, Arkansas, the sum of benzene, tolu-

Dosimetry and Ex posure A ssessment of Jet-Propulsion F uel 8 21 ene, ethylbenzene, and xylenes (BTEX) measurements was about 14% of the JP-8 fingerprint value; at Pope Air Force Base in North Carolina, the BTEX sum was about 50% of the JP-8 fingerprint value. The ranges of postexposure values overlapped substantially between exposed and unexposed subjects. It is often difficult to distinguish between exposed and unexposed workers on the basis of the JP-8 fingerprint, and simple division into highly exposed, moderately exposed, and unexposed workers appears to be an inadequate way to correlate adverse health effects with JP-8 body burden. About 10% of subjects had a markedly elevated JP-8 body burden. The reasons for their high exposures were not known. In addition to measurement of the JP-8 fingerprint, benzene and naphtha- lene were measured in end-exhaled breath and with passive personal monitors attached to the clothing just below the chin (Egeghy and Rappaport 2001). Preliminary results showed that median postexposure benzene concentrations in exhaled air were 4.6, 9.0, and 11.4 :g/m3 for the low-, moderate-, and high- exposure groups, respectively, and overall range was less than 1.5 to 153 :g/m3 . Preliminary results showed that the median postexposure naphthalene concentrations in exhaled air were less than 0.73, 0.93, and 1.83 :g/m3 in the low-, moderate-, and high-exposure groups, respectively, and the overall range was less than 0.5 to 15.8 :g/m3. Overall, the median postexposure concentra- tions exceeded the median preexposure concentrations by about 2- to 3-fold. Naphthalene concentrations were higher than benzene concentrations in the environmental breathing-air samples; the opposite was true for exhaled-air samples. That could be related to lower volatility and higher expected blood:air partition coefficient for naphthalene. The best correlation between the environmental and exhaled-air concentrations was obtained for the high- exposure group (with large variability); however, this correlation was weak for the low- and moderate-exposure groups. Both correlations were stronger for naphthalene than for benzene. Benzene, naphthalene, and hydroxynaphthalene metabolites were mea- sured in urine before and after exposure (Serdar et al. 2001). Urinary concen- trations of benzene and naphthalene may be good surrogates of internal expo- sure because they reflect inhalation and skin exposure. Preliminary results indicated that, in the high-exposure group, there was strong correlation be- tween workplace air and exhaled-air concentrations of each of these chemicals. A high correlation was also observed for urinary naphthalene and its metabo- lite. Urinary concentrations of these chemicals were higher in smokers, but the effect of smoking became less significant as the exposure to JP-8 in- creased. That air and preexposure urine samples did not show a positive correlation suggests that preexposure urinary benzene and naphthalene con- centrations were the result of sources other than occupational exposures.

22 Toxicologic A ssessment of Jet-Propulsion F uel 8 PROTEIN ADDUCTS AS SURROGATE BIOMARKERS OF JP-8 EXPOSURE Naphthalene in exhaled air and its metabolites in urine have been used as a surrogate marker of JP-8, although naphthalene constitutes only a small fraction of the hydrocarbon content of JP-8 (Serdar et al. 2001; Egeghy and Rappaport 2001). Because the majority of inhaled naphthalene is eliminated rapidly, this represents an assessment of only acute exposure to naphthalene and provides no information on long-term steady-state exposure to JP-8. Protein (specifically, albumin and hemoglobin) adducts of reactive metabolites of naphthalene (such as 1, 2-, and 1,4-naphthoquinones) were measured as possible surrogate markers of long-term JP-8 exposure in Air Force personnel involved in fuel-cell maintenance (Waidyanatha and Rappaport 2001). Prelimi- nary results showed that 1,2-naphthoquinone albumin adduct (NQ-Ab) con- centrations in blood were slightly greater in personnel exposed to JP-8 than in referent (unexposed) subjects (Waidyanatha and Rappaport 2001). Hemo- globin adducts were not detected. The correlation between NQ-Ab adducts and workplace naphthalene concentrations was not statistically significant. Given the long half-life of albumin and the measurement of protein adducts after only a single day of exposure, the lack of statistical correlation was not unexpected. The data showed that NQ-Ab may be a marker of long-term exposure to JP-8; however, an estimate of exposure over several days is neces- sary to validate the use of this marker for chronic exposure to JP-8. FACTORS THAT MODIFY INTERNAL DOSE OF JP-8 Dermal Absorption Because JP-8 is a complex mixture of hydrocarbons of widely varying vapor pressure and lipophilicity, uptake by the dermal route is highly affected by the physicochemical properties of the mixture. After dermal application to uncovered skin, individual volatile components may evaporate from the skin surface or penetrate the skin and pass into the venous blood for distribution throughout the body. For substances of low molecular weight, volatile com- pounds evaporate preferentially. Less-volatile, longer-chain hydrocarbons tend to be hydrophobic (i.e., they have a larger log Kow ). Low volatility dic- tates prolonged skin contact, and the higher hydrophobicity leads to faster dermal penetration. Direct applications of JP-8 to skin produces higher skin and systemic exposures to the higher-molecular-weight components of the distillate mixture.

Dosimetry and Ex posure A ssessment of Jet-Propulsion F uel 8 23 Several JP-8 additives exhibit high dermal penetration. Using static diffu- sion cells with excised, denuded F-344 rat skin, Garrett et al. (1999) demon- strated a steady-state flux of 41.4 :g/cm2 per hour with the following constit- uents: diethylene glycol monomethylether (DiEGME) > dodecane > methylnaphthalene > trimethyl benzene > undecane > naphthalene > decane > ethylbenzene > nonane > tridecane. Riviere et al. (1999) studied the sys- temic absorption and cutaneous distribution of JP-8 across isolated porcine skin flap. Overall percutaneous absorption of dodecane, hexadecane, and naphthalene was inversely related to skin deposition and was influenced by the fuel type and performance additives. Dermal absorption of jet fuel was com- plicated by the presence of different patterns of binding to the stratum corneum and subcutaneous fat. Riviere et al. (1999) estimated that if both hands were constantly wet with JP-8, about 17 mg of hydrocarbons would penetrate systemically through skin. Baynes et al. (2001) evaluated the influ- ence of JP-8 performance additives on the absorption of JP-8 components. They used porcine skin flaps to characterize chemical-biologic interactions that modulate diffusion of various JP-8 components in vitro. Isolated perfused porcine skin flaps were employed to evaluate diffusion in a model system with viable vasculature. Several performance additives in JP-8 increased the reten- tion of various JP-8 components (e.g., naphthalene and dodecane) on the skin surface. Performance additives, such as DiEGME, may bind to some compo- nents of JP-8 and can increase their dermal retention. This could reduce over- all systemic absorption of JP-8 fuel during short-term exposure. However, overall systemic absorption may be greater over long periods of continuous dermal contact because of a persistent dermal retention. Inhalation Exposure Air Force personnel are most likely to be exposed to JP-8 vapors, although mixed vapor and aerosol exposures may occur during aircraft cold starts or specialized situations such as when the fuel is sprayed as a dust sup- pressant (CDC 1999). Inhalation of JP-8 vapors or aerosols will result in respiratory tract deposition and systemic absorption of some fuel components. Inhaled vapors, even those with high volatility and low water solubility, may be largely absorbed in the nasal cavity rather than in the lungs, although significant lung uptake may also occur (Dahl 1989). Following vapor deposi- tion, the extent of systemic absorption depends on the blood:air partition coefficients for the individual fuel components. Monooxygenase-mediated metabolism in the nose, and to a lesser extent in the lung, may activate certain aromatic components of JP-8, possibly resulting in toxic effects at the site of

24 Toxicologic A ssessment of Jet-Propulsion F uel 8 deposition. Repeated inhalation of JP-8 may result in activation of metabolic enzymes in the respiratory tract and, therefore, have an impact on the extent of production of both nontoxic and toxic metabolites. Monooxygenase-medi- ated metabolism is not expected to have a major effect on JP-8 aliphatic com- ponents. Nasal exposures have been implicated as an important source of JP- 8 exposure because metabolites of toluene and xylene have been shown to accumulate in nasal mucosa and olfactory bulbs of mice exposed to toluene and xylene by inhalation (Ghantous 1990). It is generally believed that greater overall deposition of JP-8 might occur following inhalation of respirable aerosols, due to the presence of more high- molecular-weight compounds, compared to that occurring upon vapor inhala- tion. As with vapors, systemic absorption may occur following deposition. The sites of respiratory tract deposition will vary depending on aerosol particle size and whether oral or nasal breathing occurs. For example, for an aerosol particle with a mass median aerodynamic diameter of 3 mm, approximately 60% will deposit in the nose and 10-15% in the pulmonary region in a nasal breathing human. With oral breathing, approximately 80% will deposit in the pulmonary region. The extent of overall respiratory tract deposition drops dramatically to approximately 40% with particle sizes less than 1 mm. Oral Exposure Although of questionable relevance for determining or assessing a PEL for JP-8, oral-toxicity studies with fuels have the advantage of administering the sample without prior fractionation of components. However, other fac- tors related to fractional absorption, oral uptake rates, metabolic clearance, and tissue storage of the individual components lead to differential systemic doses of individual components that might influence toxicity. ASSESSING DOSIMTERY IN TOXICOLOGY STUDIES JP-8 is a complex distillate fuel and, therefore, specific exposure scenarios in the workplace, in controlled human studies, and in experimental animal toxicology studies can lead to preferential enhancement of high- or low-vola- tility components of the fuel. When evaluating human and animal toxicology studies, it is important to know how exposures in workers, volunteers, or animals were generated from liquid JP-8. The process used to generate spe- cific atmospheres of JP-8 will cause enrichment of specific groups of com-

Dosimetry and Ex posure A ssessment of Jet-Propulsion F uel 8 25 pounds. When describing exposures to JP8, the relationship of various expo- sure routes and their consequences for altered absorption of low- or high- volatility compounds in the fuel should be specified. This section provides background information on the consequences of different exposure routes in altering absorbed doses of JP-8 fuel components. This information is relevant to interpreting dosing scenarios used in animal toxicity studies and exposures in occupational studies. Inhalation studies using JP-8 are complicated because the atmosphere may contain a mixture of vapor constituents and liquid-droplet aerosols of fuel. Many of the procedures for atmospheric generation lead to fractionation of the fuel, which may be problematic because there is differential toxicity of fuel components. There are methods of atmosphere generation of vapors that preserve the composition of the original fuel. One method involves heating the fuel in a tube to achieve complete volatilization before introduction of vapor into the experimental chamber atmosphere. This procedure produces vapor atmospheres with a composition similar to that of the fuel. Another method of atmosphere generation involves bubbling air or nitrogen through the fuel and transporting the resulting atmosphere to the exposure chamber. Both of these systems require care to ensure that the final chamber atmo- sphere does not contain aerosols created by vigorous agitation of the liquid fuel or condensation of the vapors after cooling of the atmosphere. The latter method will generally produce an atmosphere that is enriched with the lower-molecular-weight, more-volatile compounds in the chamber atmosphere compared to the original fuel. Achieving high concentrations of JP-8 in an exposure chamber requires introduction of a mixture of vapor and aerosol. The size of the aerosol parti- cles determines the lung region where they preferentially deposit. The compo- sition of the aerosol droplets will depend on the methods used for their gener- ation and the “age” and physical characteristics of the aerosol. An aerosol generated from fuel should initially be similar in composition to fuel. As time passes, the preferential volatilization of low-molecular-weight components produces an aerosol enriched in the longer-chain, higher-molecular-weight components. The extent of enrichment depends both on the time that elapses between the production of the aerosol and its presentation in the breathing zone of the subjects and on the residence time of aerosol in the chamber. Aerosol exposure can lead to inhalation of vapors enriched in the low- molecular-weight components and to surface deposition of liquid droplets enriched in higher-molecular-weight n-alkanes within the respiratory tract. The above considerations should serve as a guide to the reader as data from human and animal toxicity studies are presented in subsequent chapters.

26 Toxicologic A ssessment of Jet-Propulsion F uel 8 CONCLUSIONS AND RECOMMENDATIONS Occupational exposure to JP-8 occurs primarily during transportation and storage of the fuel, aircraft fueling and defueling, maintenance of aircrafts, cold engine starts and performance testing, and operation and maintenance of other Air Force equipment and machinery. The Air Force personnel working in aircraft fuel-cell maintenance shops and fuel-specialty and fuel-transporta- tion shops are probably at greatest risk for exposure to JP-8. Because fuel tanks with cross ventilation have much lower concentrations of JP-8 than fuel tanks with poor ventilation, the subcommittee recommends that the Air Force properly cross-ventilate fuel tanks when personnel are working in them. The subcommittee concludes that in addition to inhalation exposure, the potential exists for a substantial contribution to overall JP-8 exposure by the dermal route, including mucous membranes and the eyes, either by contact with vapors and aerosols or by direct skin contact with JP-8. Therefore, the subcommittee recommends that the PEL adopted by the Air Force have a skin notation. The subcommittee also recommends that dermal exposures of Air Force personnel to JP-8 be minimized by the use of appropriate protective clothing or other measures. It further recommends that the Air Force evalu- ate the effectiveness of various protective clothing for personnel who are likely to come into contact with JP-8 and that it use the most effective protective clothing. Because there is the potential for substantial exposure of troops to JP-8 when it is used to suppress desert sand and as a method of obscuring troops and equipment, the subcommittee recommends that the DOD no longer use JP-8 for those purposes. The commercial airline jet fuel, Jet A, is similar in composition to JP-8, although JP-8 contains several additives not included in Jet A. Jet A is used widely in commercial aircraft, and the exposed cohort is large; however, the subcommittee did not find epidemiologic studies of this cohort. The subcom- mittee recommends that an epidemiologic study of commercial airline employ- ees exposed to Jet A be conducted to characterize their exposures and to determine whether any health effects are associated with Jet A exposure. Because there is evidence that aerosols are more toxic than vapors, the subcommittee recommends development of an analytic method to distinguish between aerosol and vapor exposures in occupational settings. Finally, the subcommittee recommends that the Air Force monitor the workplace where JP-8 is being used to ensure that exposure to vapors and aerosols does not exceed safe levels.

Dosimetry and Ex posure A ssessment of Jet-Propulsion F uel 8 27 REFERENCES ATSDR (Agency for Toxic Substances and Disease Registry). 1998. Toxicological Profile for Jet Fuels (JP-5 and JP-8). U.S. Department of Health and Human Services, Pub lic Health Service, Agency for Toxic Su bstances and Disease R egis- try, Atlanta, GA. Bayne s, R.E., J.D. Brooks, K. Budsaba, C.E. Smith, and J.E. Riviere. 2001. M ixture effects of JP-8 additives on the dermal disposition of jet fuel components. Toxicol. Appl. Pharmacol. 175(3):269-281. Carlton, G.N ., and L.B. Sm ith. 2000. Exposures to jet fuel and benzene during air- craft fuel tank repair in the U.S. Air Force. App l. Occup. Environ. Hyg. 15(6):485-491. CDC (Centers for D isease C ontrol an d Preven tion). 1999. Background Document on Gulf War-Related Research for the Health Impact of Chemical Exposures During the Gulf War: Research Planning Conference. Public Health Service, Bethesda, MD (as cited in C heng et al. 2001). Cheng, Y.S., Y. Zhou, J. Chow, J. Watson , and C. Frazier. 2001. Chem ical com posi- tion of aerosol from kerosene heaters burning jet fuels. Aerosol. Sci. Technol. 35:949-957. Dahl, A.R . 1989. Metabolic characteristics of the respiratory trac t. Pp. 141-160 in Con cepts in Inhalation Toxicology, R.O. McClellan, and R.F. Henderson, eds. New York: H em isphe re Publishing Co. Egeghy, P., and S. Rappaport. 2001. Measurement of benzene and naphthalene in air and breath in the U.S. Air Force as an indicator of JP8 exposure. Pp. 38-54 in JP8 Final Risk Assessment. The Institute of Environmental and Human Health (TIEHH), Lubbock, TX. August 2001. Garrett, C.M., D.L. Pollard, T.E. Miller, and J.N. M cDo ugal. 1999. In vitro dermal absorption of jet fuel (JP-8) and its com ponents. Conference T opics in Toxicol- ogy and Risk Assessment 12-15 April 1999, Wright-Patterson AFB, OH. Ghantous, H., L. Dencker, J. Gabrielsson, B.R. Danielsson, and K. Bergman. 1990. Accumulation and turnover of m etabolites of toluene and xylene in nasal mucosa and olfactory bulb in the mouse. Pharmacol. Toxicol. 66(2):87-92. Gibson, R., J. Pleil, S. Smith, and D . Toschlog. 2001. Assessm ent of JP8 in blood. Pp. 29-31 in JP8 Final Risk Assessment. The Institute of Environmental and Hum an Health (TIEHH), Lubbock, TX. August 2001. Henz, K. 19 98. Survey of Jet Fuels Proc ured by the Defense Energy Support Center, 1990-1996. Defense Logistics Agencies, Ft. Belvior, VA. Nylander-French, L.A ., and J.D. Arch er. 2001. Qu antification of derma l exposu re to jet fuel, risk assessment of acute exposure to jet fuel. Pp. 25-28 in JP8 Final Risk Assessment. The Institute of E nvironmental and Human Health (TIEH H), Lubbock, TX. August 2001. Pleil, J.D. 2001. Direct measurement of total body burd en of JP 8 jet fuel (breath), risk assessment of acute exposu re to jet fuel. Pp. 32-37 in JP8 Final Risk Assess-

28 Toxicologic A ssessment of Jet-Propulsion F uel 8 ment. The Institute of Environmental and Human H ealth (TIEHH), Lubbock, TX. August 2001. Pleil, J.D., L.B. Smith, and S.D. Zelnick. 2000. Personal exposure to JP-8 jet fuel vapors and exhaust at air force bases. Environ. Health Perspect. 108(3):183-192. Riviere, J.E., J.D. Broo ks, N.A. Monteiro-Riviere, K. Budsaba, and C.E. Smith. 1999. Dermal absorption and distribution of topically dosed jet fuels jet-A, JP-8, and JP- 8(10 0). To xicol. App l. Pharmacol. 160(1):60-75. Serdar, B., P.P. Egeghy, and S.M. Rappaport. 2001. Urinary benzene, naphthalene, 1- and 2-hyd roxynaph thalene as biom arkers of acute (short-term ) exposure to JP8. Pp. 57-64 in JP 8 Final Risk Assessm ent. The Institute of Environmental and Human H ealth (TIEHH), Lubbock, TX. August 2001. TIEHH (The Institute of Environmental and Human Health). 2001. JP8 Final Risk Assessme nt. The Institute of Environmental and Human Health, Lubbock, TX. August 2001. 179pp. Ullrich, S.E. 1999. De rm al application of JP-8 fuel induces immune suppression. Toxicol. Sci. 52(1):61-67. Waidyanatha, S., and S.M. Rappapot. 2001. Protein add ucts as biomarkers of expo- sure to jet fuel. Pp. 121-178 in JP8 Final Risk Assessment. The Institute of Environmental and Human H ealth (TIEHH), Lubbock, TX. August 2001. Witten, M. 2002. JP-8 jet fuel: An overview. [Online] Available: http://ww w.jp8.org [accessed O ctober 1, 2002]. Wolfe, R.E., E.R. Kinead , M.L . Feld mann, H.F . Lea hy, and W.W. Jederberg. 1997. Acu te Toxicity Evaluation of JP-8 Jet Fuel and JP-8 Jet Fuel C ontaining Addi- tives. Govt. Rep. Announce Index (GRA &I) Issue 09. Yeung, P., A. Rogers, and B. Davies. 1997. Safe working in aircraft fuel tanks: An Australian experience. Appl. Occup. Environ. Hyg. 12(9):587-594. Zhou, Y., and Y.S. Cheng. 2000. Characterization of emission from kerosine heaters in an unvented tent. Aerosol Sci. Technol. 33:510-524.

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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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