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2 Jet Propellant Fuels 5 and 81 Acute Exposure Guideline Levels PREFACE Under the authority of the Federal Advisory Committee Act (FACA) P.L. 92-463 of 1972, the National Advisory Committee for Acute Exposure Guide- line Levels for Hazardous Substances (NAC/AEGL Committee) has been estab- lished to identify, review, and interpret relevant toxicologic and other scientific data and develop AEGLs for high-priority, acutely toxic chemicals. AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 minutes (min) to 8 hours (h). Three levels—AEGL-1, AEGL-2, and AEGL-3—are developed for each of five exposure periods (10 and 30 min and 1, 4, and 8 h) and are distin- guished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows: AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory 1 This document was prepared by the AEGL Development Team composed of Sylvia Talmage (Summitec Corporation) and John Hinz (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances. The NAC reviewed and revised the document and AEGLs as deemed necessary. Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC committee has concluded that the AEGLs developed in this document are scientifically valid conclusions based on the data reviewed by the NRC and are consistent with the NRC guidelines reports (NRC 1993, 2001). 72

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73 Jet Propellant Fuels 5 and 8 effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure. AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including sus- ceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape. AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including sus- ceptible individuals, could experience life-threatening health effects or death. Airborne concentrations below the AEGL-1 represent exposure concentra- tions that could produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, nonsen- sory effects. With increasing airborne concentrations above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL. Although the AEGL values represent threshold levels for the general public, including susceptible subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic responses, could experience the effects described at concentrations below the correspond- ing AEGL. SUMMARY Jet propellant (JP) fuels, used in military and civilian aircraft, are complex mixtures of aliphatic and aromatic hydrocarbons made by blending various dis- tillate stocks of petroleum. The primary military fuel for land-based military aircraft is JP-8; this fuel replaces JP-4, which is no longer in use. JP-5 was de- veloped by the U.S. Navy for shipboard service. The composition of JP-8 and JP-5 is basically that of kerosene (with additives), and they have similar chemi- cal and physical characteristics (ATSDR 1998). Worldwide, approximately 60 billion gallons of military JP-8 and the equivalent commercial Jet A and Jet A-1 are consumed on an annual basis. The military jet fuels contain additives that are not found in commercial jet fuels. Civilian and military personnel may be ex- posed to jet fuels during fuel production, aircraft fueling, aircraft maintenance, and accidental spills or pipeline leaks. The primary hazard associated with re- lease of jet fuels is fire and explosion. This document focuses on the toxicity of JP-8 with some attention to the chemically similar JP-5. These two fuels have a similar composition and appear to have similar toxicities (ATSDR 1998). Monitoring data indicate that expo- sures to JP-4, which has a higher vapor pressure than JP-8 and JP-5, were higher than those associated with JP-8 and JP-5. Data were located on acute sensory and systemic effects of JP-8 and JP-5 in mice and rats; subchronic toxicity stud- ies have addressed systemic and pulmonary toxicity. For both fuels, eye irrita-

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74 Acute Exposure Guideline Levels tion was observed at concentrations of ≥ 2,500 mg/m3. Mild skin irritation was observed after direct topical application. Several short-term and repeated expo- sure studies addressed the toxicity of jet fuel aerosols. Exposure to aerosolized jet fuels was associated with enhanced toxicity compared with equivalent expo- sure to fuel vapors, the lungs and immune system being the target organs. How- ever, emergency exposures are expected to be in the form of vapor exposures that result from spills, whereas aerosols are relevant only to occupational expo- sures during aircraft-foam removal operations or aircraft cold starts. Studies that addressed the toxicity of jet fuel only in the aerosolized form were not used to derive AEGL values (Martin et al. 2010; Tremblay et al. 2010). The data col- lected during aerosol inhalation studies are included in this technical support document (TSD) for completeness. Animal studies also examined potential neu- rotoxicity, developmental and reproductive toxicity, and carcinogenicity. The JP fuels are not considered genotoxic or carcinogenic and, in a preliminary study, JP-8 failed to cause spermatotoxic effects in humans. A characteristic nephropa- thy and resulting renal cancer, specific to male rats exposed to jet fuels, is not relevant to humans. Concentrations of jet fuels of ≥ 2,500 mg/m3 also induce central nervous system (CNS) depression. Many of the components of jet fuels are lipophilic solvents. In general, the lipophilic solvents that induce CNS de- pression attain steady state in the blood within an hour. The AEGL-1 was based on the sensory irritation study of Whitman and Hinz (2001) wherein an RD50 (the concentration that reduced the respiratory rate of Swiss-Webster mice by 50%) was measured for JP-8 vapor plus aerosol at 2,876 mg/m3. The RD50 test is a standard protocol (ASTM E981-84 [1988]) for estimating sensory irritancy of airborne chemicals. Groups of four male Swiss- Webster mice were exposed for 30 min at 681, 1,090, 1,837, or 3,565 mg/m3. Reductions in the respiratory rate within 30 min were concentration-dependent, and breathing patterns were characteristic of upper airway sensory irritation. On the basis of a correlation between the RD50 and sensory irritancy concentrations for a large number of structurally diverse chemicals, a 10-fold reduction of the RD50 results in a concentration that elicits sensory irritation in humans but that can be tolerated for hours to days (Alarie 1981; Schaper 1993). Irritation is con- centration-dependent, and there is adaptation to the mild sensory irritation that characterizes the AEGL-1. Using this reasoning, the resulting concentration of 290 mg/m3 can be tolerated at each AEGL-1 exposure duration. The 290 mg/m3 value is supported by the lack of adverse health effects in subchronic toxicity animal studies with repeated or continuous exposures to JP-8 vapor at 1,000 mg/m3 (Mattie et al. 1991; Briggs 2001; Rossi et al. 2001). The AEGL-2 is based on inhalation studies with rats and mice demonstrat- ing that exposure to JP-8 at 1,100 mg/m3 failed to elicit signs of intoxication or CNS depression. The shorter-term studies (30 min to 4 h) with exposures to JP-8 or JP-5 in mixed vapor and aerosol forms at 3,430-5,000 mg/m3 (MacEwen and Vernot 1985; Wolfe et al. 1996; Whitman and Hinz 2001) with support from studies using repeated or continuous vapor exposures at 1,000 mg/m3 (Mattie et al. 1991; Briggs 2001; Rossi et al. 2001) were used as the basis for the AEGL-2.

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75 Jet Propellant Fuels 5 and 8 No uncertainty factors were applied to the results of studies at the 1,000 mg/m3 concentration because no adverse effects were observed, and the exposures were repeated or continuous for up to 90 days. The higher concentrations of JP-8 (3,430, 3,565, and 4,440 mg/m3) and of JP-5 (5,000 mg/m3) were divided by an interspecies factor of 1 (compared with humans, systemic uptake is greater in rodents based on higher respiration rate and cardiac output) and by an intraspe- cies uncertainty factor of 3 to protect potentially sensitive individuals. An in- traspecies uncertainty factor of 3 is considered adequate because the thresholds for both sensory irritation and CNS depression for solvents in humans and ro- dents do not generally differ by more than 3-fold. The lower value, 1,100 mg/mg3, in the resulting range of values, 1,100-1,700 mg/m3, is approximately the same concentration as in the no-adverse-effect repeated-exposure studies. CNS depression is a concentration-related effect. For solvents that cause CNS effects, steady state is generally approached within 1 h. In addition, because the exposure duration in the key study was 4 h, the 1,100 mg/m3 value was used for the 4-h and shorter time periods. Because the exposure of rats and mice at 1,000 mg/m3 was continuous (24 h/day) for up to 90 days (Mattie et al. 1991), the 1,100-mg/m3 value can also be used for the 8-h AEGL. The fact that the expo- sures in most of these studies, especially at the higher concentrations, were to mixed JP-8 vapor and aerosols supports the AEGL-2 values. Because of their relatively low vapor pressure, the physical properties suggest JP-8 and JP-5 might not attain a sustained vapor concentration high enough to cause death. As reported by Wolfe et al. (1996), the highest vapor concentration of JP-8 that could be attained under an experimental system at 35ºC was 3,430 mg/m3, and the highest vapor and aerosol concentration that could be generated was 4,440 mg/m3. However, the highest vapor and aerosol attainable under ambient concentrations has been estimated at 700 mg/m3, and 500 mg/m3 is the upper bound for a stable JP-8 aerosol. Based on the likelihood that airborne concentrations of JP-8 or JP-5 aerosol and vapor sufficient to cause death cannot be sustained under ambient conditions, an AEGL-3 was not de- rived. Although the AEGL values are based on reported mixed aerosol and vapor concentrations of jet fuels, the primary exposure is to the vapor. Exposure to aerosols will probably result in deep lung deposition. Therefore, AEGLs based on mixed aerosol and vapor exposures are more conservative than those based on gas-phase exposures. Aerosol concentrations of 10 mg/m3 result in a visible cloud. These concentrations and higher will result in liquid deposition on sur- faces. AEGL values are summarized in Table 2-1 below. I. INTRODUCTION Jet propellant or jet propulsion (JP) fuels are used in military aviation for turbine engine and jet aircraft. Jet fuels are complex mixtures of aliphatic and

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76 Acute Exposure Guideline Levels aromatic hydrocarbons made by blending petroleum distillates, such as naphtha (the low boiling fraction of petroleum), gasoline, and kerosene to meet military or commercial specifications (U.S. Air Force 1989). Jet fuels are composed of aliphatic, monocyclane, aromatic, and alkene hydrocarbons in the C5 to C16 range. Aliphatic alkanes (paraffins) and cycloalkanes (naphthenes) are the major constituents (75-90%) of kerosene (Cavender 1994a,b,c; reviewed in ATSDR 1998). The boiling range for jet fuels is usually well above that of benzene and n-hexane. Conversely, the maximum final boiling point of middle distillate fuels tends to exclude the presence of high-boiling polycyclic aromatic hydrocarbons. The composition of jet fuels varies depending on the type of crude oil from which the fuel is derived, the refining process used, and the additives. Additives include antioxidants, metal deactivators, corrosion or icing inhibitors, and elec- trical conductivity agents (reviewed in ATSDR 1998). The major vapor-phase hydrocarbon components of JP-8 are listed in Appendix A. TABLE 2-1 Summary of AEGL Values for JP-5 and JP-8a,b End Point Classification 10 min 30 min 1h 4h 8h (Reference) AEGL-1 290 290 290 290 290 Slight sensory (nondisabling) mg/m3 mg/m3 mg/m3 mg/m3 mg/m3 irritation in humans (extrapolated from mouse RD50 test) (Whitman and Hinz 2001) AEGL-2 1,100 1,100 1,100 1,100 1,100 No clinical signs mg/m3 mg/m3 mg/m3 mg/m3 mg/m3 (disabling) during repeated exposures at 1,000 mg/m3 to rats and mice (Mattie et al. 1991; Briggs 2001; Rossi et al.. 2001); sensory irritation at >3,430 mg/m3 in rats and mice (Wolfe et al. 1996; Whitman and Hinz 2001) No datac AEGL-3 Not Not Not Not Not (lethal) determined determined determined determined determined a The values apply to JP-8 vapor or vapor and aerosol and not to the pure aerosol. b The values apply to JP-8 vapor and not to JP-8+100. c A lethal concentration was not attained in the available toxicity studies; the low vapor pressures of JP-8 and JP-5 may preclude attainment of a lethal concentration. Abbreviation: RD50, concentration that reduces the respiratory rate by 50%.

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77 Jet Propellant Fuels 5 and 8 The present document focuses on the toxicity of JP-8, the jet fuel used by the U.S. military. Information on JP-5 (used by the Navy for shipboard aircraft) is included in this document because, chemically, JP-5 can be considered a sub- set of JP-8 (ATSDR 1998; Potter and Simmons 1998). Both JP-8 and JP-5 are middle distillates with boiling ranges of 150-275°C. JP-8 contains alkane carbon ranging from n-C8 through n-C17; whereas JP-5 contains carbons ranging from n-C7 through n-C18 (Potter and Simmons 1998). Prior to 1979, JP-4—a naphtha- based, wide-cut fuel made from straight-run, desulfurized kerosene blended with lower boiling distillates or made by blending refined shale oil distillates (ATSDR 1995)—was used by the Air Force. JP-4 was replaced by JP-8 in 1994, and JP-8 is now the standardized fuel for the U.S. military. Thus, the human monitoring and animal toxicity studies with JP-4 are not discussed in this docu- ment. Data on JP-7, a specialized high-altitude fuel restricted to reconnaissance aircraft (MacNaughton and Uddin 1984), are not included since JP-7 is no longer used. JP-5 is a turbine engine fuel developed by the U.S. Navy for use aboard aircraft carriers because of its lower volatility and lower post-crash fire hazard compared with JP-4 (ATSDR 1998). JP-5 has a specified distillation tempera- ture of 205°C for the 10% recovery point to 290°C for the end point (Military Specification MIL-T-5624K [1976]). The U.S. Naval Service is anticipating transition from the nearly exclusive use of JP-5 to predominant use of JP-8, con- sistent with the other military services and the militaries of most NATO coun- tries. Compared with JP-4, the less volatile JP-8 contains alkanes in the C8 to C17 range. In a survey of JP-8 fuels, the average aromatic content was 14.5%, the highest aromatic content reported being 18.8% (Martel 1989). The composi- tion (v/v) of JP-8 consists of approximately 9% C8 to C9 aliphatic hydrocarbons, approximately 65% C10 to C14 aliphatic hydrocarbons, approximately 7% C15 to C17 aliphatic hydrocarbons, and approximately 18% aromatic hydrocarbons (NRC 1996; Carlton and Smith 2000). Typical aromatic hydrocarbons include benzene, ethylbenzene, toluene, and xylenes, but the distillation fraction of JP-8 minimizes the presence of benzene and related low-boiling aromatic hydrocar- bons. Ambient air samples in aircraft fuel tank maintenance areas are dominated by C9 to C12 n-alkanes; the primary n-alkanes in these samples are nonane (C9), decane (C10), and undecane (C11) (Pleil et al. 2000). The benzene content is 0.005% by volume (Carlton and Smith 2000). The typical aromatic hydrocar- bons in JP-8 are the polycyclic aromatics and not the lighter aromatics, such as benzene, toluene, xylenes, and ethyl benzene found in gasoline (Appendix A). Only the studies of Carlton and Smith (2000) discuss benzene exposures measured during maintenance operations on military aircraft fuel tanks. The exposures occur inside the fuel tanks or with personnel removing foam from the tanks. The latter operation involves the generation of aerosols as the foam is pulled out of the fuel tank. Benzene is more water soluble than other jet fuel components, and some benzene remains in the small amount of water present after many refuelings. This amount can result in measurable benzene concentra-

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78 Acute Exposure Guideline Levels tions during these operations even though the levels of benzene in the bulk fuel are not detectable (see Appendix A). Benzene is not a component of concern for JP-8 AEGLs. Except for additives included to meet military specifications, JP-8 is simi- lar to international jet fuels A and A-1, the former used in U.S. commercial air- craft. JP-8 contains antioxidants, static inhibitors, corrosion inhibitors, fuel sys- tem icing inhibitors, lubrication improvers, biocides, and thermal stability improvers (Military Specification MIL-T-5624P [1992]). According to the Navy Environmental Health Center, additives to JP-8 typically compose <2% of the volume (NEHC 2001). Addition of antioxidants—such as 2,6-di-tert-butyl-4- methylphenol—or metal deactivators—such as N,N-disalcylidene-1,2- propanediamine—is optional. Static dissipaters—such as Stadis 450 (50-60% toluene)—organic acid corrosion inhibitors (8Q21), and icing inhibitors—such as diethylene glycol monomethyl ether—are required. JP-5 differs in that an antioxidant is required and a metal deactivator and static dissipater are not used. To improve the thermal stability of JP-8, a proprietary package of addi- tives including an antioxidant (butylated hydroxytoluene), a metal deactivator (N,N-disalicylal-1,2-propane diamine), and a detergent and dispersant (8Q405) are added at concentrations of 100-300 ppm. The resulting fuel is called JP-8+100 (Wolfe et al. 1996; Kornguth 1998). JP-8+100 is not widely used at present. The chemical identification and chemical and physical properties of JP-8 and JP-5 are summarized in Table 2-2. Many of the physical properties of JP-8, such as autoignition temperature (229ºC), and flammability and explosive limits, both 0.7%-5%, are identical to those of kerosene (ATSDR 1998). The flashpoint is 38ºC, indicating that fire is the major hazard associated with jet fuels. Because of the complex and variable composition of jet fuels, the molecular weight is expressed as an average, and concentrations are expressed in terms of their total hydrocarbon content measured in mass units (mg/m3). Worldwide, approximately 60 billion gallons of JP-8 and commercial Jet A and Jet A-1 are consumed each year (Armbrust Aviation Group 1998). An- nual use of JP-8 by the U.S. military services and North Atlantic Treaty Organi- zation forces is estimated at 4.5 billion gallons (Zeiger and Smith 1998). The U.S. military utilization of JP-8 and JP-5 exceeds 2.2 billion gallons per year (Henz 1998). In addition to fueling aircraft and tanks, the military uses JP-8 for heating tents and buildings. Exposure to jet fuels can occur during production and refining, monitoring of storage tanks, aircraft fueling and defueling, spills during handling, and leaks at storage facilities. Under some conditions, aircraft jettison excess fuel into the upper atmosphere (ATSDR 1998; Rossi et al. 2001). Annually, several hundred thousand military personnel are involved in these operations. Thus, exposure to JP-8 represents the largest single source of chemical exposure in the U.S. mili- tary (Pleil et al. 2000); civilian exposure is restricted to the chemically similar Jet A used in commercial aircraft.

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79 Jet Propellant Fuels 5 and 8 TABLE 2-2 Chemical and Physical Data for Jet Fuels 8 and 5 Parameter Data Reference Synonyms JP-8 Kerosene, aviation kerosene, fuel oil ATSDR 1998, number 1, jet kerosene, turbo fuel A, NRC 1996, Chevron straight run kerosene, distillate fuel Phillips 2009a oil-light, MIL-T-83133D, AVTUR, NATO F-34 JP-5 Kerosene, MIL-T-5624N Chevron Phillips 2008 Molecular formula Not applicable Structure Not applicable Molecular weight (mean) JP-8 167, 180 MacNaughton and Uddin 1984 JP-5 168, 170, 185 NIOSH 2005; NRC 1996 CAS Registry Number 8008-20-6a/70892-10-3b JP-8 ATSDR 1998 8008-20-6a/70892-10-3b JP-5 ATSDR 1998 Physical state JP-8 Clear-to-light amber liquid ATSDR 1998; Richie et al. 2001a JP-5 Clear liquid ATSDR 1998 Solubility in water JP-8 5 mg/L (kerosene) ATSDR 1998 JP-5 5 mg/L (kerosene) ATSDR 1998 Density (specific gravity) JP-8 0.81 g/mL Potter and Simmons 1998 JP-5 0.82 g/mL Potter and Simmons 1998 Vapor pressure JP-8 1.8 mmHg (28°C) NRC 1996 0.4-3.3 mmHg (20°C) SwRI 2001 JP-5 5.9-26.4 mmHg (kerosene) ATSDR 1998 1.8 mmHg (28°C) NRC 1996 Vapor density, JP-8 (air = 1) 4.5-5 Ritchie et al. 2001a Explosive limits, JP-8 Lower explosive limit 0.7-0.9% Ritchie et al. 2001a Upper explosive limit 5-6% Flash point JP-8 37.8°C Chevron Phillips 2010 JP-5 60°C Chevron Phillips 2009b (Continued)

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80 Acute Exposure Guideline Levels TABLE 2-2 Continued Parameter Data Reference Liquid density (water = 1) JP-8 0.788-0.845 kg/L ATSDR 1998 JP-5 0.788-0.845 kg/L ATSDR 1998 Melting point JP-8 −52ºC ATSDR 1998 JP-5 −46ºC ATSDR 1998 Boiling range JP-8 150-275ºC Potter and Simmons 1998 JP-5 150-275ºC Potter and Simmons 1998 Conversion factors (STP)c ≈ 8 mg/m3 JP-8 1 ppm NRC 1996 1 mg/m3 ≈ 0.12 ppm ≈ 8.3 mg/m3 JP-5 1 ppm NRC 1996 1 mg/m3 ≈ 0.12 ppm a The CAS Reg. No. is that of kerosene. b The CAS Reg. No. is that of fuel oil no. 1. c Conversion factors at standard temperature and pressure (STP) are based on the average molecular weight. 2. HUMAN TOXICITY DATA At sufficiently high exposures, liquid and vapor JP-8 may be irritating to the eyes and skin. Dermal exposure may cause defatting, drying, and irritation of the skin (U.S. Air Force 1989). Topical exposure can induce skin inflammation, which has been documented by morphologic and ultrastructural changes (ATSDR 1998; McDougal and Rogers 2004; Monteiro-Rivere et al. 2004). Workers exposed to jet fuels have complained of dizziness, headache, nausea, and fatigue (NRC 1996; ATSDR 1995, 1998). Aspiration of the liquid fuel into the lungs can give rise to chemical pneumonitis. The toxicity data of various jet fuels have been summarized and reviewed in IARC (1989), ATSDR (1995, 1998), Bruckner and Warren (2001), Ritchie et al. (2001a, 2003), and NRC (2003). Past exposures to concentrations as high as 3,000 mg/m3 were to the more volatile JP-4 and equivalents (Knave et al. 1978; Martone 1981). Increased complaints of dizziness and fatigue have been associ- ated with these concentrations. The low vapor pressure of JP-8 and JP-5 and the moderately high average molecular weights indicate that their relatively low volatility is such that a systemic health risk from vapor inhalation is unlikely (ACGIH 2009). In its toxicologic assessment of JP-8, the NRC (2003, pp. 4-5) noted: “No relevant adverse effects were observed for hepatotoxicity, renal tox- icity, and cardiovascular toxicity, although the exposure concentrations did not

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81 Jet Propellant Fuels 5 and 8 exceed 1,000 mg/m3. Adequate studies have not been conducted to assess the potential toxicity of inhaled JP-8 for reproductive toxicity, developmental toxic- ity, and genotoxicity”. 2.1. Acute Lethality No reports of humans fatalities associated with JP-8 or JP-5 exposure were located in the available literature. 2.2. Nonlethal Toxicity The odor thresholds of JP-8 and JP-5 have been reported at 1 ppm and 0.082 ppm, respectively. The odor is described as similar to that of kerosene (ATSDR 1998). Olsen (1998) compared liver function, kidney and hematopoietic system function, serum proteins, neurocognitive function, and general physical health of 18 Air Force personnel exposed to jet fuels with 18 nonexposed subjects. The exposed subjects were evaluated while exposed to JP-4 and at 3, 6, and 18 months after JP-8 replaced JP-4. Exposure to naphthas was <3 ppm. Benzene concentrations were 0.05 ppm during exposure to JP-4 and nondetectable during exposure to JP-8. No significant differences were found between exposed and nonexposed subjects with regard to liver and kidney function, frequency of symptoms, or general physical health. Two of the subjects exposed to JP-8 de- veloped a rash on their hands. After 18 months of exposure to JP-8, several he- matopoietic parameters were affected in that exposed workers had lower mean corpuscular volume and mean corpuscular hemoglobin and higher mean corpus- cular hemoglobin concentration (smaller cells with a higher concentration of hemoglobin) than the nonexposed subjects. Norseth et al. (1998) measured circulating serum alanine aminotransferase (formerly called serum glutamic pyruvic transaminase) and serum aspartate amino transferase (formerly called serum glutamic oxaloacetic transaminase), and glutathione transferase liver enzyme activities as an indicator of liver dam- age in Norwegian crew chiefs exposed to JP-8. Exposures were to C5-C9 ali- phatic hydrocarbons at 0.13 ppm and to C9-C13 at 3.11 ppm. Compared with controls, there were no meaningful differences between the two groups. 2.2.1. Clinical Studies Because JP-8 is a kerosene-based fuel, the results of human exposures to kerosene offer useful comparisons. When six volunteers (age range 23-49 years) inhaled several different concentrations of deodorized kerosene, the odor thresh- old was 0.6 mg/m3 (0.09 ppm) (Carpenter et al. 1976). The kerosene consisted

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82 Acute Exposure Guideline Levels of 55.2% paraffins, 40.9% naphthenes, and 3.9% aromatics and had a boiling range of 208-272°C. There were no complaints of irritation or discomfort when six volunteers (age range 20-63 years) were exposed to a measured concentra- tion of 140 mg/m3 (20 ppm) for 15 min. Three of the volunteers experienced slight olfactory fatigue. The authors reported that 14,000 mg/m3 is the highest obtainable vapor concentration of deodorized kerosene at 25°C. 2.2.2. Accidental Exposures Two individuals were exposed for 1 h to an unknown concentration of JP- 5 in the cockpit of an unpressurized aircraft (Porter 1990). The odor was de- scribed as “overwhelming”, and the individuals experienced burning eyes and euphoria (one individual) during exposure and complaints of headache, nausea, coordination difficulties, and transient memory defects after exposures were made. The effects subsided within 24 h in one individual and within 4 days in the other. 2.2.3. Monitoring Data Because of its wide use in the past, most published monitoring data in- volve JP-4. Because of its higher volatility than JP-8, ambient air concentrations of JP-4 at military installations were higher than the currently measured concen- trations of JP-8. Measured concentrations of JP-4 jet fuel inside aircraft shelters at bases ranged from 33 to 3,090 mg/m3 and were dependent on temperature and shelter size. Concentrations of the less volatile JP-8 averaged <20 mg/m3 at three shelters. Refueling normally took 3-5 min, although in one case, aircraft refueling associated with a measured exposure concentration of JP-4 at 620 mg/m3 took 30 min (Martone 1981). At Swedish and Danish military bases where aviation fuel was equivalent to JP-4, maximum 5-min workplace concen- trations ranged up to 3,226 mg/m3 (Knave et al. 1978), and 8-h time-weighted averages (TWAs) ranged up to 3,000 mg/m3 (Knave et al. 1978; Thomas and Richardson 1981; Holm et al. 1987; Døssing et al. 1985; Selden and Ahlborg 1986, 1987). Vapor concentrations often exceeded 350 mg/m3 (a specific expo- sure duration was not given) (Selden and Ahlborg 1986, 1987); exposure dura- tions to unspecified concentrations ranged up to 31 years (Døssing et al. 1985). Workplace air concentration data for JP-8 and JP-5 are summarized in Ta- ble 2-3. The highest concentrations of JP-8 were measured inside empty aircraft fuel tanks during maintenance and foam removal. Workers who enter the fuel tanks wear a supplied air respirator or a self-contained breathing apparatus, whereas the outside attendants do not. Therefore, information on potential ad- verse health effects (from JP-8 and JP-5 inhalation) could not be derived from these studies.

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129 Jet Propellant Fuels 5 and 8 McInturf, S.M., M.Y. Bekkedal, G.D. Ritchie, A.F. Nordholm, and J. Rossi. 2001. Ef- fects of repeated JP-8 exposure on eyeblink conditioning in humans [abstract]. Toxicologist 60(1):555. Mihic, S.J., S.J. McQuilkin, E.I. Eger, P. Ionescu, and R.A. Harris. 1994. Potentiation of γ-aminobytyric acid type A receptor-mediated chloride currents by novel halo- genated compounds correlates with their abilities to induce general anesthesia. Mol. Pharmacol. 46(5):851-857. Monteiro-Riviere, N., A. Inman, and J. Riviere. 2001. Effects of short-term high-dose and low-dose dermal exposure to Jet A, JP-8 and JP-8 + 100 jet fuels. J. Appl. Toxicol. 21(6):485-494. Monteiro-Riviere, N., A. Inman, and J.E. Riviere. 2004. Skin toxicity of jet fuels: Ultra- structural studies and the effects of substance P. Toxicol. Appl. Pharmacol. 195(3):339-347. NAVOSH (Navy Occupational Safety and Health). 1992. Interim Recommendations for Permissible Fuel Exposure Criteria from the Navy Environmental Health Center’s Navy Occupational Safety and Health (NAVOSH) Standards Update Board. Memorandum 6261, Ser 34/2514. Navy Environmental Health Center, Norfolk, VA. April 9, 1992 . NEHC (U.S. Navy Environmental Health Center). 1993. Industrial Hygiene Field Opera- tions Manual. Technical Manual NEHC-TM91-2. U.S. Navy Environmental Health Center, Norfolk, VA. NEHC (U.S. Navy Environmental Health Center). 2001. Fuels Comparison Chart. U.S. Navy Environmental Health Center, Norfolk, VA. October 2001 [online]. Avail- ble: http://www-nehc.med.navy.mil/downloads/ep/fuels_comp_chart.pdf [accessed Oct. 11, 2010]. Nessel, C.S. 1999. A comprehensive evaluation of the carcinogenic potential of middle distillate duels. Drug Chem. Toxicol. 22(1):165-180. Nilsen, O.G., O.A. Haugen, K. Zahlsen, J. Halganset, A. Helseth, H. Aarset, and I. Eide. 1988. Toxicity of n-C9 to n-C13 alkanes in the rat on short term inhalation. Phar- macol. Toxicol. 62(5):259-266. NIOSH (National Institute for Occupational Safety and Health). 1996. Documentation for Immediately Dangerous to Life or Health Concentrations (IDLH): NIOSH Chemical Listing and Documentation of Revised IDLH Values (as of 3/1/95)- Petroleum Distillates (Naphtha). U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. August 1996 [online]. Available: http://www.cdc.gov/niosh/ idlh/8002059.html [accessed Oct. 11, 2010]. NIOSH (National Institute for Occupational Safety and Health). 2005. NIOSH Pocket Guide to Chemical Hazards: Kerosene. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Oc- cupational Safety and Health, Cincinnati, OH. September 2005 [online]. Avail- able: http://www.cdc.gov/niosh/npg/npgd0366.html [accessed Oct. 11, 2010]. Norseth, T., L. Toftegaard, and O. Romerike. 1998. Measures of Liver Function in Nor- wegian Crewchiefs. Presented at the International Conference on the Environ- mental Health and Safety of Jet Fuel, April 1-3, 1998, San Antonio, TX. NRC (National Research Council). 1993. Guidelines for Developing Community Emer- gency Exposure Levels for Hazardous Substances. Washington, DC: National Academy Press. NRC (National Research Council). 1996. Permissible Exposure Levels for Selected Mili- tary Fuel Vapors. Washington DC: National Academy Press.

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130 Acute Exposure Guideline Levels 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). 2003. Toxicologic Assessment of Jet-Propulsion Fuel 8. Washington, DC: The National Academies Press. NTP (National Toxicology Program). 1986. Toxicology and Carcinogenesis Studies of Marine Diesel Fuel and JP-5 Navy Fuel (CAS No. 8008-20-6) in B6C3F1 Mice (Dermal Studies). NTP TR 310. NIH 86-2566. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Toxicology Program, Research Triangle Park, NC. Olsen, D.M. 1998. Occupational Assessment of Air Force Personnel Exposure to Jet Fuel Before and After Conversion to JP-8. Presented at the International Confer- ence on the Environmental Health and Safety of Jet Fuel, April 1-3, 1998, San An- tonio, TX. Parton, K.H., J. Pfaff, A.M. Hays, and M. Witten. 1993. Effects of JP-8 jet fuel inhalation on the liver of F-344 rats. Toxicologist 13:48. Pedersen, L.M., K. Larsen, and K.H. Cohr. 1984. Kinetics of white spirit in human fat and blood during short-term experimental exposure. Act Pharacol. Toxicol. 55(4): 308-316. Perbellini, L., F. Brugnone, D. Caretta, and G. Maranelli. 1985. Partition coefficients of some industrial aliphatic hydrocarbons (C5-C7) in blood and human tissues. Br. J. Ind. Med. 42(3):162-167. Perleberg, U.R., D.A. Keys, and J.W. Fisher. 2004. Development of a physiologically based pharmacokinetic model for decane, a constituent of jet propellent-8. Inhal. Toxicol. 16(11-12):771-783. Pfaff, J., K. Parton, R. Lantz, H. Chen, D. Carter, and M. Witten. 1992. Effects of JP-8 jet fuel exposure on pulmonary function [abstract]. Am. Rev. Respir. Dis. 145 (4 Part 2):A89. Pfaff, J., G. Parliman, K. Parton, R. Lantz, H. Chen, M. Hays, M. Witten. 1993. Patho- logic changes after JP-8 jet fuel inhalation in Fischer 344 rats [abstract]. FASEB J. 7:A408. Pfaff, J., K. Parton, R.C. Lantz, H. Chen, A.M. Hays, and M.L. Witten. 1995. Inhalation exposure to JP-8 jet fuel alters pulmonary function and substance P levels in Fischer 344 rats. J. Appl. Toxicol. 15(4):249-256. Pfaff, J.K., B.J. Tollinger, R.C. Lantz, H. Chen, A.M. Hays, and M.L. Witten. 1996. Neu- ral endopeptidase (NEP) and its role in pathological pulmonary change with inha- lation exposure to JP-8 jet fuel. Toxicol. Ind. Health 12(1):93-103. 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. Porter, H.O. 1990. Aviators intoxicated by inhalation of JP-5 fuel vapors. Aviat. Space Environ. Med. 61(7):654-656. Potter, T.L., and K.E. Simmons. 1998. Composition of Petroleum Mixtures. Hydrocarbon Working Group Series Vol. 2. Amherst, MA: Amherst Scientific Publishers. Puhala, E., G. LeMasters, L. Smith, G. Talaska, S. Simpson, J. Joyce, K. Trinh, and J. Lu. 1997. Jet fuel exposure in the United States Air Force. Appl. Occup. Environ. Hyg. 12(9):606-610. Rhodes, A.G., G.K. LeMasters, J.E. Lockey, J.W. Smith, J.H. Yiin, R. Gibson, and S. Rap- paport. 2001. The effects of JP8 on immune cell counts of tank entry workers. Pp. 100-120 in JP-8 Final Risk Assessment Report, R.K. Kendall, Ernest Smith, L.B. Smith, and R.L. Gibson, eds. IOH-RS-BR-SR-2005-0003. Texas Tech University,

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132 Acute Exposure Guideline Levels Stokholm, J. and K.H. Cohr. 1979. Exposure of Humans to White Spirit. III. Concentra- tions in Alveolar Air and Venous Blood during Experimental Exposure [in Danish with English Summary]. Institute of Occupational Health Report No. 3/1979. Co- penhagen: Danish National Labour Inspection Service. Struwe, G., B. Knave, and P. Mindus. 1983. Neuropsychiatric symptoms in workers occupationally exposed to jet fuel - a combined epidemiological and casuistic study. Acta. Psychiatr. Scand. Suppl. 303:55-67. Swenberg, J.A. 1993. α2u-Globulin nephropathy: Review of the cellular and molecular mechanisms involved and their implications for human risk assessment. Environ. Health Perspect. 101(Suppl. 6):39-44. SwRI (Southwest Research Institute). 2001. JP-8 Volatility Study. IERA-RS-BR-SR- 2001-0002. Southwest Research Institute, San Antonio, TX. March 2001. Tardif, R., G. Charest-Tardif, J. Brodeur, and K. Krishnan. 1997. Physiologically based pharmacokinetic modeling of a ternary mixture of alkyl benzenes in rats and hu- mans. Toxicol. Appl. Pharmacol. 144(1):120-134. Thomas, T.C., and A. Richardson III. 1981. An infrared analysis method for the determi- nation of hydrocarbons collected on charcoal tubes. Pp. 37-48 in Chemical Haz- ards in the Workplace, G. Choudhary, ed. ACS Symposium Series 149. Washing- ton, DC: American Chemical Society. Tremblay, R.T., S.A. Martin, and J.W. Fisher. 2010. Novel characterization of the aerosol and gas-phase composition for aerosolized jet fuel atmospheres. Inhal. Toxicol. 22(5):394-401. Ullrich, S.E. 1999. Dermal application of JP-8 jet fuel induces immune suppression. Toxicol. Sci. 52(1):61-67. Ullrich, S.E., and H.E. Lyons. 2000. Mechanisms involved in the immunotoxicity in- duced by dermal application of JP-8 jet fuel. Toxicol. Sci. 58(2):290-298. University of California. 2006. Researchers Reveal Lung's Unique Innate Immune Sys- tem. Science Daily, April 19, 2006 [online]. Available: http://www.sciencedaily. com/releases/2006/04/060419073650.htm [accessed Oct. 12, 2010]. U.S. Air Force. 1989. The Installation Restoration Program Toxicology Guide, Volume 4. ADA215002. Prepared by Oak Ridge National Laboratory, Oak Ridge, TN, for the Air Force Systems Command, Wright-Patterson Air Force Base, OH. Whitman, F.T., and J.P. Hinz. 2001. Sensory Irritation Study in Mice: JP-4, JP-8, JP- 8+100. Report No. IERA RS-BR-SR-2001-0005. ADA398112. Air Force Institute for Environment, Safety and Occupational Health Risk Analysis, Brooks Air Force Base TX [online]. Available: http://www.dtic.mil/cgi-bin/GetTRDoc?AD=ADA 398112&Location=U2&doc=GetTRDoc.pdf [accessed Oct. 13, 2010]. Witschi, H.R., and J.A. Last. 2001. Toxic responses of the respiratory system. Pp. 515- 534 in Casarett & Doull’s Toxicology: The Basic Science of Poisons, 6th Ed., C.D. Klaassen, ed. New York: McGraw-Hill. Witten, M.L. 1994. The Chronic Effects of JP-8 Jet Fuel Exposure on the Lungs. Techni- cal Report, AFOSR-TR-940382. ADA280982. University of Arizona, Tucson, AZ. Witten, M.L., S.E. Leeman, R.C. Lantz, P.M. Joseph, C.H. Burke, W.K. Jung, D. Quinn, and C.A. Hales. 1990. Chronic jet fuel exposure increases lung substance P (SP) concentration in rabbits. P. 29 in Substance P and Related Peptides: Cellular and Molecular Physiology, S.E. Leeman, ed. International Symposium, University of Massachusetts and the New York Academy of Science, New York. Witten, M.L., J.K. Pfaff, K. Parton, R.C. Lantz, D. Carter, and S.E. Leeman. 1992. JP-8 jet fuel exposure alters lung chemical mediator and substance P activity in rats [ab- stract]. FASEB J. 6:A1065.

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133 Jet Propellant Fuels 5 and 8 Witzmann, F.A., M.D. Bauer, A.M. Fieno, R.A. Grant, T.W. Keougth, S.E. Kornguth, M.P. Lacey, F.L. Siegel, Y. Sun, L.S. Wright, R.S. Young, and M.L. Witten. 1999. Proteomic analysis of simulated occupational jet fuel exposure in the lung. Elec- trophoresis 20(18):3659-3669. Witzmann, F.A., R.L. Carpenter, G.D. Ritchie, C.L. Wilson, A.F. Nordholm, and J. Rossi III. 2000a. Toxicity of chemical mixtures: Proteomic analysis of persisting liver and kidney protein alterations induced by repeated exposure of rats to JP-8 jet fuel vapor. Electrophoresis 21(11):2138-2147. Witzmann, F.A., M.D. Bauer, A.M. Fieno, R.A. Grant, T.W. Keougth, M.P. Lacey, Y. Sun, M.L. Witten, and R.S. Young. 2000b. Proteomic analysis of the renal effects of simulated occupational jet fuel exposure. Electrophoresis 21(5):976-984. Witzmann, F.A., A. Bobb, G.B. Briggs, H.N. Coppage, R.A. Hess, J.Y. Li, N.M. Pedrick, G.D. Ritchie, J. Rossi III, and K.R. Still. 2003. Analysis of rat testicular protein expression following 91-day exposure to JP-8 jet fuel vapor. Proteomics 3(6):1016-1027. Wolfe, R.E., E.R. Kinkead, M.L. Feldmann, H.F. Leahy, W.W. Jederberg, K.R. Still, and D.R. Mattie. 1996. Acute Toxicity Evaluation of JP-8 Jet Fuel and JP-8 Jet Fuel Containing Additives. AL/OE-TR-1996-0136. NMRI-94-114. Prepared by Man- Tech Environmental Technology, Inc., Dayton, OH, for Armstrong Laboratory, Occupational and Environmental Health Directorate, Toxicology Division, Wright-Patterson AFB, OH. Young, R.S., and M.L. Witten. 2000. Age Related Alterations in Pulmonary Function and Pulmonary Lipid Peroxidation After Exposure to JP-8 and JP-8+100 Blend Jet Fuel. Presented at the AFOSR JP-8 Jet Fuel Toxicology Workshop, January 11-12, 2000, University of Arizona, Tucson, AZ. Zahlsen, K., A.M. Nilsen, I. Eide, and O.G. Nilsen. 1990. Accumulation and distribution of aliphatic (n-nonane), aromatic (1,2,4-trimethylbenzene) and napthenic (1,2,4- trimethylcyclohexane) hydrocarbons in the rat after repeated inhalation. Pharma- col. Toxicol. 67(5):436-440. Zahlsen, K., I. Eide, A,M, Nielsen, and O.G. Nilsen. 1992. Inhalation kinetics of C6 to C10 aliphatic, aromatic and naphthenic hydrocarbons in rat after repeated expo- sures. Pharmacol. Toxicol.71(2):144-149. Zeiger, E., and L. Smith. 1998. The first international conference on the environmental health and safety of jet fuel. Environ. Health Perspect. 106(11):763-764.

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134 Acute Exposure Guideline Levels APPENDIX A INDIVIDUAL HYDROCARBON DATA—NEAT JET FUELS,a PERCENT BY VOLUME TABLE A-1 Hydrocarbon Data for Jet Fuels 4, 8, and 8+100 Hydrocarbon JP-4 JP-8 JP-8+100 Isopentane 0.1437 ND ND n-Pentane 0.3237 ND ND 2-Methylpentane 0.7302 ND ND 3-Methylpentane 0.4139 ND ND n-Hexane 1.5403 0.0011 0.0023 Methylcyclopentane 1.3913 0.0006 0.0014 Benzene 0.3551 ND ND Cyclohexane 1.7803 0.0033 0.0030 3-Methylhexane 1.5065 0.0119 0.0078 Isooctane 2.4941 0.0256 0.0112 n-Heptane 3.3458 0.0481 0.0357 Toluene 2.0009 0.0721 0.0664 3-Methylheptane 0.9567 0.0604 0.0524 n-Octane 3.8056 0.2609 0.2506 Ethylbenzene 0.6458 0.1414 0.1322 p-, m-Xylene 3.3541 0.6610 0.6319 n-Nonane 1.5714 0.9103 0.8886 Cumene 0.1870 0.1756 0.1672 Propylbenzene 0.1830 0.2846 0.2698 p-, m-Ethyltoluene 0.5318 0.6921 0.6801 1,3,5-Trimethylbenzene 0.5948 1.0785 1.0677 o-Ethyltoluene 0.4586 0.8522 0.8416 1,2,4-Trimethylbenzene 0.8171 1.2355 1.2192 n-Decane 1.2687 2.8907 2.8641 n-Undecane 1.7350 5.5171 5.5065 n-Dodecane 1.8808 5.3191 5.3032 n-Tetradecane 1.4537 3.0523 3.0658 n-Hexadecane 0.3169 0.7690 0.7602 Total analytesb 35.7868 24.0634 23.8289 a Source: Whitman and Hinz 2001, p. 46. b Percent of test substance analyzed; other hydrocarbons unidentified.

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135 Jet Propellant Fuels 5 and 8 APPENDIX B CATEGORY GRAPH OF TOXICITY DATA AND AEGL VALUES Chemical Toxicity - Acute Animal Data JP-5 and JP-8 10000 AEGL-2 1000 No Effect AEGL-1 Discomfort mg/m3 100 Disabling 10 Some Lethality Lethal 1 0 60 120 180 240 300 360 420 480 AEGL Minutes FIGURE 2-1 Category graph for JP-5 and JP-8. Note: Only acute studies are graphed. TABLE B-2 Data Used in Category Graph mg/m3 Categorya Source Species Minutes NAC/AEGL-1 290 10 AEGL NAC/AEGL-1 290 30 AEGL NAC/AEGL-1 290 60 AEGL NAC/AEGL-1 290 240 AEGL NAC/AEGL-1 290 480 AEGL NAC/AEGL-2 1,100 10 AEGL NAC/AEGL-2 1,100 30 AEGL NAC/AEGL-2 1,100 60 AEGL NAC/AEGL-2 1,100 240 AEGL NAC/AEGL-2 1,100 480 AEGL (Continued)

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136 Acute Exposure Guideline Levels TABLE B-2 Continued mg/m3 Categorya Source Species Minutes NAC/AEGL-3 ND 10 AEGL NAC/AEGL-3 ND 30 AEGL NAC/AEGL-3 ND 60 AEGL NAC/AEGL-3 ND 240 AEGL NAC/AEGL-3 ND 480 AEGL Whitman and Mouse 681 30 1: 22% Hinz 2001 depression, respiratory rate Whitman and Mouse 1,090 30 1: 38% Hinz 2001 depression, respiratory rate Whitman and Mouse 1,837 30 2: 46% Hinz 2001 depression, respiratory rate Whitman and Mouse 3,565 30 2: 50% Hinz 2001 depression, respiratory rate Whitman and Mouse 708 (vapor) 30 1: 28% Hinz 2001 depression, respiratory rate Wolfe et al. 1996 Rat 3,430 (vapor) 240 2: Eye, upper respiratory tract irritation Wolfe et al. 1996 Rat 4,440 (2,630 240 2: No deaths vapor + 1,810 aerosol) MacEwen and Rat 2,500 60 2: Eye irritation Vernot 1985 MacEwen and Rat 5,000 60 2: CNS Vernot 1985 depression a Categories: 0, no effect; 1, discomfort; 2, disabling; and 3, lethal. Abbreviations: ND, not determined; CNS, central nervous system.

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137 Jet Propellant Fuels 5 and 8 APPENDIX C ACUTE EXPOSURE GUIDELINE LEVELS FOR JP-5 AND JP-8 Derivation Summary for JP-5 AND JP-8 AEGL-1 VALUES 10 min 30 min 1h 4h 8h 3 3 3 3 290 mg/m3 290 mg/m 290 mg/m 290 mg/m 290 mg/m Key reference: Whitman, F.T., and J.P. Hinz. 2001. Sensory Irritation Study in Mice: JP-4, JP-8, JP-8+100. Report No. IERA RS-BR-SR-2001-0005. ADA398112. Air Force Institute for Environment, Safety and Occupational Health Risk Analysis, Brooks Air Force Base TX. Supporting reference: MacEwen, J.D., and E.H. Vernot. 1985. Investigation of the 1-h emergency exposure limit of JP-5. Pp. 137-144 in Toxic Hazards Research Unit Annual Report: 1985. AAMRL-TR-85-058. AD-A161558. Aerospace Medical Research Laboratory, Wright-Patterson Air Force Base, OH. Test species/Strain/Number: Mouse/Swiss-Webster/4 per group Exposure route/Concentrations/Durations: Inhalation concentrations at 681, 1,090, 1,837, 3,565 mg/m3 (vapor + aerosol), and 708 mg/m3 (vapor only) for 30 min Effects: 681 mg/m3: 22% decrease in respiratory rate 1,090 mg/m3: 38% decrease in respiratory rate 1,837 mg/m3: 46% decrease in respiratory rate 3,565 mg/m3: 50% decrease in respiratory rate 708 mg/m3: 28% decrease in respiratory rate (vapor-only exposure) 2,876 mg/m3: calculated RD50 End point/Concentration/Rationale: 290 mg/m3 across all AEGL-1 exposure durations (0.1 times the calculated mouse RD50 of 2,876 mg/m3 [slight irritation withstood for hours,according to Alarie 1981]) Uncertainty factors/Rationale: Total uncertainty factor: Not applicable. (The mouse RD50 was reduced by a factor of 10, which reduces the sensory irritation to a concentration tolerated for hours to days by most individuals.) The factor of 10 is the same as applying interspecies and intraspecies uncertainty factors of 3 each. Interspecies: Not applicable Intraspecies: Not applicable Modifying factor: Not applied Animal-to-human dosimetric adjustment: Not applied Time-scaling: Not applied; the repeated nature of many of the studies ensures the safety of a single exposure. (Continued)

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138 Acute Exposure Guideline Levels AEGL-1 VALUES Continued 10 min 30 min 1h 4h 8h 3 3 3 3 290 mg/m3 290 mg/m 290 mg/m 290 mg/m 290 mg/m Data adequacy: The database of inhalation and oral studies in rodents is robust. Studies addressed irritation, neurotoxicity, immunotoxicity, developmental and reproductive effects, genotoxicity, and carcinogenicity. Human exposures to JP-8 were limited to occupational exposures; monitoring studies with other aviation fuels showed few effects. The value is supported by animal studies in which repeated and continuous exposures at 1,000 mg/m3 for up to 90 days failed to elicit clinical signs or adverse health effects. Interspecies and intraspecies uncertainty factors of 1 and 3, respectively would result in a similar value, 330 mg/m3. AEGL-2 VALUES 10 min 30 min 1h 4h 8h 3 3 3 3 1,100 mg/m3 1,100 mg/m 1,100 mg/m 1,100 mg/m 1,100 mg/m Key references: Briggs, G.B. 2001. Evaluation of Military Fuel Potential to Produce Male Reproductive Toxicity. Presented at the International Conference on the Environmental Health and Safety of Jet Fuel, August 8-11, 2001, San Antonio, TX. MacEwen, J.D., and E.H. Vernot. 1985. Toxic Hazards Research Unit Annual Report: 1985. AAMRL-TR-85-058. ADA161558. Aerospace Medical Research Laboratory, Wright-Patterson Air Force Base, OH. Mattie, D.R., C.L. Alden, T.K. Newell, C.L. Gaworski, and C.D. Flemming. 1991. A 90-day continuous vapor inhalation toxicity study of JP-8 jet fuel followed by 20 or 21 months of recovery in Fischer 344 rats and C57BL/6 mice. Toxicol. Pathol. 19(2):77-87. Rossi, J., III, A.F. Nordholm, R.L Carpenter, G.D. Ritchie, and W. Malcomb. 2001. Effects of repeated exposure of rats to JP-5 or JP-8 jet fuel vapor on neurobehavioral capacity and neurotransmitter levels. J. Toxicol. Environ. Health A 63(6):397-428. Whitman, F.T., and J.P. Hinz. 2001. Sensory Irritation Study in Mice: JP-4, JP-8, JP-8+100. Report No. IERA RS-BR-SR-2001-0005. ADA398112. Air Force Institute for Environment, Safety and Occupational Health Risk Analysis, Brooks Air Force Base TX. Wolfe, R.E., E.R. Kinkead, M.L. Feldmann, H.F. Leahy, W.W. Jederberg, K.R. Still, and D.R. Mattie. 1996. Acute Toxicity Evaluation of JP-8 Jet Fuel and JP-8 Jet Fuel Containing Additives. AL/OE-TR-1996-0136. NMRI-94-114. Prepared by ManTech Environmental Technology, Inc., Dayton, OH, for Armstrong Laboratory, Occupational and Environmental Health Directorate, Toxicology Division, Wright- Patterson AFB, OH. Test species/Strain/Number: Rat/F344/groups of 5 to 95 Mouse/Swiss-Webster/4 per group (Continued)

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139 Jet Propellant Fuels 5 and 8 AEGL-2 VALUES Continued 10 min 30 min 1h 4h 8h 3 3 3 3 1,100 mg/m3 1,100 mg/m 1,100 mg/m 1,100 mg/m 1,100 mg/m 3 Exposure route/Concentrations/Durations: 3,430-5,000 mg/m for 30 min to 4 h (vapor + aerosol); 1,000 mg/m3 for up to 90 days. The exposure at 5,000 mg/m3 involved JP-5, which is similar in composition to JP-8. Effects: 3,430 mg/m3: eye and upper respiratory irritation (Wolfe et al. 1996) 3,565 mg/m3: no clinical signs; respiratory rate depression of 50% (Whitman et al. 2001) 4,440 mg/m3: eye and upper respiratory irritation (Wolfe et al. 1996) 5,000 mg/m3: eye irritation and signs of CNS depression (MacEwen and Vernot 1985; Mattie et al. 1991) 1,000 mg/m3: no severely adverse effects (Briggs 2001; Rossi et al. 2001; and others) End point/Concentration/Rationale: Weight of evidence from all studies; escape might be impeded at the highest concentration of 5,000 mg/m3. Uncertainty factors/Rationale: Total uncertainty factor: 3 applied to concentrations of 3,430-5,000 mg/m3; 1 applied to 1,000 mg/m3 Interspecies: 1 applied to all concentrations; rodent uptake is greater than human uptake based on higher respiratory rate and cardiac output and higher blood:air partition coefficients. Intraspecies: 3 applied to 3,430-5,000 mg/m3 (1,100 mg/m3); no susceptible populations identified; upper respiratory sensory irritation and threshold for CNS effects do not differ by more than 3-fold in the general population; 1 applied to repeated exposures of 1,000 mg/m3 because no adverse health effects identified. Modifying factor: Not applied Animal-to-human dosimetric adjustment: Not applied Time-scaling: Not applied; CNS depression is a concentration threshold effect. The repeated nature of many of the studies ensures the safety of a single exposure. Data adequacy: Robust database of inhalation and oral studies in rodents that addressed irritation, neurotoxicity, immunotoxicity, developmental and reproductive effects, genotoxicity, and carcinogenicity. Human exposures to JP-8 were limited to occupational exposures; monitoring studies with other aviation fuels showed few effects. AEGL-3 VALUES 10 min 30 min 1h 4h 8h Not Not Not Not Not determined determined determined determined determined Data adequacy: There are no data on lethal concentrations.