JP-8 Exposure Research Articles

Personal Exposure to JP-8 Jet Fuel Vapors and Exhaust at Air Force Bases

JP-8 jet fuel (similar to commercial/international jet A-1 fuel) is the standard military fuel for all types of vehicles, including the U.S. Air Force aircraft inventory. As such, JP-8 presents the most common chemical exposure in the Air Force, particularly for flight and ground crew personnel during preflight operations and for maintenance personnel performing routine tasks. Personal exposure at an Air Force base occurs through occupational exposure for personnel involved with fuel and aircraft handling and/or through incidental exposure, primarily through inhalation of ambient fuel vapors. Because JP-8 is less volatile than its predecessor fuel (JP-4), contact with liquid fuel on skin and clothing may result in prolonged exposure. The slowly evaporating JP-8 fuel tends to linger on exposed personnel during their interaction with their previously unexposed colleagues. To begin to assess the relative exposures, we made ambient air measurements and used recently developed methods for collecting exhaled breath in special containers. We then analyzed for certain volatile marker compounds for JP-8, as well as for some aromatic hydrocarbons (especially benzene) that are related to long-term health risks. Ambient samples were collected by using compact, battery-operated, personal whole-air samplers that have recently been developed as commercial products; breath samples were collected using our single-breath canister method that uses 1-L canisters fitted with valves and small disposable breathing tubes. We collected breath samples from various groups of Air Force personnel and found a demonstrable JP-8 exposure for all subjects, ranging from slight elevations as compared to a control cohort to > 100 [mutilpe] the control values. This work suggests that further studies should be performed on specific issues to obtain pertinent exposure data. The data can be applied to assessments of health outcomes and to recommendations for changes in the use of personal protective equipment that optimize risk reduction without undue impact on a mission.

Personal exposure to JP-8 jet fuel vapors and exhaust at air force bases.

JP-8 jet fuel (similar to commercial/international jet A-1 fuel) is the standard military fuel for all types of vehicles, including the U.S. Air Force aircraft inventory. As such, JP-8 presents the most common chemical exposure in the Air Force, particularly for flight and ground crew personnel during preflight operations and for maintenance personnel performing routine tasks. Personal exposure at an Air Force base occurs through occupational exposure for personnel involved with fuel and aircraft handling and/or through incidental exposure, primarily through inhalation of ambient fuel vapors. Because JP-8 is less volatile than its predecessor fuel (JP-4), contact with liquid fuel on skin and clothing may result in prolonged exposure. The slowly evaporating JP-8 fuel tends to linger on exposed personnel during their interaction with their previously unexposed colleagues. To begin to assess the relative exposures, we made ambient air measurements and used recently developed methods for collecting exhaled breath in special containers. We then analyzed for certain volatile marker compounds for JP-8, as well as for some aromatic hydrocarbons (especially benzene) that are related to long-term health risks. Ambient samples were collected by using compact, battery-operated, personal whole-air samplers that have recently been developed as commercial products; breath samples were collected using our single-breath canister method that uses 1-L canisters fitted with valves and small disposable breathing tubes. We collected breath samples from various groups of Air Force personnel and found a demonstrable JP-8 exposure for all subjects, ranging from slight elevations as compared to a control cohort to > 100 [mutilpe] the control values. This work suggests that further studies should be performed on specific issues to obtain pertinent exposure data. The data can be applied to assessments of health outcomes and to recommendations for changes in the use of personal protective equipment that optimize risk reduction without undue impact on a mission.

INVESTIGATION OF IN VITRO TOXICITY OF JET FUELS JP-8 AND JET A

The in vitro cytotoxicity and electrophysiological toxicity of Jet Propulsion-8 (JP-8 jet fuel) on four cell types: H4IIE liver cell line, NIH Swiss 3T3 cell line, neuroblastoma × glioma NG108-15 cells, and embryonic hippocampal neurons were investigated. H4IIE cells exposed to Jet A (a commercial fuel) and JP-8 demonstrated identical toxicity with an IC50 of 12.6 ± 0.4 μg/ml for the two fuels. Comparison of H4IIE and NIH/3T3 toxicity to JP-8 revealed that NIH/3T3 cells were more sensitive to JP-8 than H4IIE cells, with an IC50 8.5 ± 0.1 μg/ml. JP-8 exposure for the hippocampal neurons proved to be highly toxic (IC50 of <2 μg/ml), while in contrast, the NG108-15 cells were much less sensitive. Electrophysiological examination of NG108-15 cells showed that administration of JP-8 at 1 μg/ml did not alter significantly any of the electrophysiological properties. However, exposure to JP-8 at 10 μg/ml during a current stimulus of +46 pA decreased the amplitude of the action potential to 83 ± 7% (n = 4), the rate of rise, dV/dtMAX to 50 ± 8% (n = 4), and the spiking rate to 25 ± 11% (n = 4) of the corresponding control levels. These results demonstrate JP-8 induced cytotoxic varies among cell types. The possible mechanisms underlying these observations are presented.

Dermal application of JP-8 jet fuel induces immune suppression.

Chronic exposure to JP-8 jet fuel induces lung toxicity, adverse neurological effects and some liver and kidney dysfunction. In addition, inhalation of JP-8 induces immune suppression. Besides the lung, the other major route of JP-8 exposure is via the skin. In this study we tested the hypothesis that dermal exposure to JP-8 is immune suppressive. JP-8 was applied to the skin of adult female C3H/HeN mice and various immune parameters were examined. Dermal exposure to JP-8, either multiple small exposures (50 microl for 5 days) or a single large dose (250-300 microl) resulted in immune suppression. The induction of contact hypersensitivity was impaired in a dose-dependent manner regardless of whether the contact allergen was applied directly to the JP-8-treated skin or at a distant un-treated site. In addition, the generation of a classic delayed-type hypersensitivity reaction to a bacterial antigen (Borellia burgdorferi) injected into the subcutaneous space was suppressed by dermal application of JP-8 at a distant site. The ability of splenic T lymphocytes from JP-8-treated mice to proliferate in response to plate-bound monoclonal anti-CD3 was also significantly suppressed. Interleukin-10, a cytokine with potent immune suppressive activity, was found in the serum of JP-8-treated mice, suggesting that the mechanism of systemic immune suppression may involve the upregulation of cytokine release by JP-8. These findings confirm the immunosuppressive effects of JP-8 and demonstrate that dermal exposure to JP-8 is immunotoxic.

NK1-receptor activation prevents hydrocarbon-induced lung injury in mice.

Recent evidence suggests that neurokinin (NK)-receptor activation may have a protective role in maintaining lung integrity when challenged by airborne toxicants such as sulfur dioxide, ozone, acrolein, or hydrocarbons. To investigate the effect of NK1-receptor activation on hydrocarbon-induced lung injury, B6.A.D. (Ahr d/Nats) mice received subchronic exposures to JP-8 jet fuel (JP-8). Lung injury was assessed by the analysis of pulmonary physiology, bronchoalveolar lavage fluid, and morphology. Hydrocarbon exposure to target JP-8 concentrations of 50 mg/m3, with saline treatment, was characterized by enhanced respiratory permeability to 99mTc-labeled diethylenetriaminepentaacetic acid, alveolar macrophage toxicity, and bronchiolar epithelial damage. Mice administered [Sar9,Met(O2)11]substance P, an NK1-receptor agonist, after each JP-8 exposure had the appearance of normal pulmonary values and tissue morphology. In contrast, endogenous NK1-receptor antagonism by CP-96345 administration exacerbated JP-8-enhanced permeability, alveolar macrophage toxicity, and bronchiolar epithelial injury. These data indicate that NK1-receptor activation may have a protective role in preventing the development of hydrocarbon-induced lung injury, possibly through the modulation of bronchiolar epithelial function.

The First International Conference on the Environmental Health and Safety of Jet Fuel

The First International Conference on the Environmental Health and Safety of Jet Fuel

ACUTE PULMONARY RESPONSE TO INHALED JP-8 JET FUEL AEROSOL IN MICE

The pulmonary response to JP-8 jet fuel inhalation was investigated by characterizing biomarkers of lung injury, respiratory permeability, pulmonary function, and lung morphology. C57BL/6 and B6.A.D. (Ahrd/Nats) mice, aryl hydrocarbon hydroxylase nonresponsive and slow N -acetylator, were exposed to atmospheres ranging from 0 to 113 mg/m 3 of aerosolized JP-8 jet fuel for 1 h. At 24-30 h after the exposure, pulmonary function testing was performed on anesthetized animals. Respiratory permeability was measured by monitoring the pulmonary clearance of instilled 99 m Tc-labeled diethylenetriamine pentaacetate and then lungs were assigned for bronchoalveolar lavage or histopathology. Bronchoalveolar lavage fluid (BALF) was analyzed for total protein, lactate dehydrogenase (LDH), and N -acetyl--D-glucosaminidase (NAG) as well as cell number and type. Pulmonary responses to JP-8 were similar in both strains of mice. JP-8 exposure between 50 and 113 mg/m 3 caused an increase in respiratory permeability, which was accompanied by BALF increases of total protein, LDH, NAG, and alveolar macrophages. There was also a small increase in BALF neutrophils in the C57BL/6 strain. JP-8 exposures did not have an effect on pulmonary function even though histopathology showed evidence of terminal bronchiole lesions. These results indicate that the acute pulmonary response to permissible exposure levels of aerosolized JP-8 jet fuel can cause changes in respiratory permeability and BALF markers of lung injury. These changes in biochemical, cellular, and pathological parameters following JP-8 exposure provide evidence that occupational exposure to hydrocarbon fuel aerosol is more detrimental than vapor exposure.

Short-term exposure to JP-8 jet fuel results in long-term immunotoxicity.

Chronic exposure to jet fuel has been shown to have adverse effects on human liver function, to cause emotional dysfunction, to cause abnormal electroencephalograms, to cause shortened attention spans, and to decrease sensorimotor speed. Due to the decision by the United States Air Force to implement the widespread use of JP-8 jet fuel in its operations, a thorough understanding of its potential effects upon exposed personnel is both critical and necessary. Exposure to potential environmental toxicants such as JP-8 may have significant effects on host systems beyond those readily visible (i.e., physiology, cardiology, respiratory, etc.); e.g., the immune system. Previous studies have shown that short-term, low concentration JP-8 exposure had significant effects on the immune system, which should have serious consequences for the exposed host in terms of susceptibility to infectious agents. If these alterations in immune function were long-lasting, it might also result in an increased likelihood of development and/or progression of cancer, as well as autoimmune disease. In the current study, mice were exposed for 1 h/day for 7 days to a moderate (1000 mg/m3) and a high (2500 mg/m3) concentration of aerosolized JP-8 jet fuel to stimulate occupational exposures. One to 28 days after the last exposure the mice were analyzed for effects of the exposure on their immune systems. It was observed that decrease in viable immune cell numbers and immune organ weights found at 24 h after exposure persisted for extended periods of time. Further, JP-8 exposure resulted in significantly decreased immune infection, as analyzed by mitogenesis assays, which persisted for up to 4 weeks post-exposure. Thus, short-term exposure of mice to JP-8 jet fuel caused significant toxicological effects on the immune system, which were long-lasting and persistent. It appears that the immune system may be the most sensitive indicator of toxicological damage due to JP-8 exposure. Such long-term changes in immune status may have significant effects on the health of the exposed individual.

Protection from JP-8 jet fuel induced immunotoxicity by administration of aerosolized substance P.

Chronic exposure to jet fuel has been shown to cause human liver dysfunction, emotional dysfunction, abnormal electroencephalograms, shortened attention spans, and decreased sensorimotor speed. The United States Air Force has decided to implement the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Exposure to potential environment toxicants such as JP-8 may have significant effects on host physiology. Previous studies in mice have shown that short-term, low concentration JP-8 exposure had significant effects on the immune system; e.g., decreased viable immune cell numbers, decreased immune organ weights, and loss on immune function that persisted for extended periods of time (i.e., up to 4 weeks post-exposure). Previous studies have shown that JP-8 induced pulmonary dysfunction was associated with a decrease in levels of the neuropeptide substance P (SP) in lung lavage fluids. It was found that administration of aerosolized SP was able to protect exposed animals from such JP-8 induced pulmonary changes. In the current study, aerosolized SP was analyzed for its effects on JP-i induced immunotoxicity in exposed mice. It was observed that SP administration could protect JP-8 exposed animals from losses of viable immune cell numbers, but not losses in immune organ weights. Further, exposure of animals to SP inhibitors generally increased the immunotoxicity of JP-8 exposure. SP appeared to act on all immune cell populations equally as analyzed by flow cytometry, as no one immune cell population appeared to be preferentially protected by SP. Also, SP administration was capable of protecting JP-8 exposed animals from loss of immune function at all concentrations of JP-8 utilized (250-2500 mg/m3). Significantly, SP only needed to be administered for 15 minutes after JP-8 exposure, and was active at both 1 microM and 1 nM concentrations. Thus, SP administration appears to be a relatively simple and efficient means to reverse the immunotoxicity due to hydrocarbon exposure.

Immunotoxicological effects of JP-8 jet fuel exposure.

Chronic exposure to jet fuel has been shown to have adverse effects on human liver function, to cause emotional dysfunction, to cause abnormal electroencephalograms, to cause shortened attention spans, and to decrease sensorimotor speed (3-5). Due to the decision by the United States Air Force to implement the widespread use of JP-8 jet fuel in its operations, a thorough understanding of its potential effects upon exposed personnel is both critical and necessary. Exposure to potential environmental toxicants such as JP-8 may have significant effects on host systems beyond those readily visible (e.g., physiology, cardiology, respiratory, etc.); e.g., the immune system. Significant changes in immune consequences, even if short-lived, may have serious consequences for the exposed host that may impinge affect susceptibility to infectious agents. Major alterations in immune function that are long-lasting may result in an increased likelihood of development and/or progression of cancer, as well as autoimmune diseases. In the current study mice were exposed for 1h/day for 7 days to varying concentrations of aerosolized JP-8 jet fuel to simulate occupational exposures. Twenty-four hours after the last exposure the mice were analyzed for effects on their immune systems. It was observed that even at exposure concentrations as low as 100 mg/m3 detrimental effects on the immune system occurred. Decreases in viable immune cell numbers and immune organ weights were found. Jet fuel exposure resulted in losses of different immune cell subpopulations depending upon the immune organ being examined. Further, JP-8 exposure resulted in significantly decreased immune function, as analyzed by mitogenesis assays. Suppressed immune function could not be overcome by the addition of exogenous growth factors known to stimulate immune function. Thus, short-term, low concentration exposure of mice to JP-8 jet fuel caused significant toxicological effects on the immune system. It appears that the immune system may be the most sensitive indicator of toxicological damage due to JP-8 exposure, as effects were seen at concentrations of jet fuel that did not evidence change in other biological systems. Such changes may have significant effects on the health of the exposed individual.