Search

The objective of this study was to compare the dermal irritation potential of four synthetic paraffinic kerosene (SPK) fuels produced by the alcohol to jet (ATJ) process with irritation produced by petroleum-derived JP-8. ATJ SPK alternative fuels are produced by the dehydration and refining of an isobutanol or similar alcohol feedstock. Two ATJ SPK fuels were produced by Gevo, Inc.; one was produced from petrochemical sources (Gevo ATJ SPK (non-bio)) and the other was bio-derived (Gevo ATJ SPK (bio)). The remaining two ATJ SPK fuels were produced by Swedish Biofuels AB; the original formula (SB ATJ SPK (old)) and the current version (SB ATJ SPK (new)) were both tested. A score of moderately irritating, as evaluated by the Primary Dermal Irritation Index (PDII) and Descriptive Rating, was calculated for the occluded exposures to all fuels except the Gevo ATJ SPK (non-bio), which was only slightly irritating when occluded. Slightly irritating scores were calculated for all semi-occluded exposures. All fuel exposures resulted in very slight to slight remaining erythema and/or edema through study day 14. Normal handling of these ATJ SPK fuels by airmen, alone or in a 50:50 blend with petroleum-derived JP-8, is not expected to result in increased irritation beyond that of current JP-8 fuels., Prepared in collaboration with the Henry M. Jackson Foundation for the Advancement of Military Medicine, Wright-Patterson AFB, OH, WIL Research, Ashland, OH, and the University of Dayton Research Institute, Wright-Patterson AFB, OH.

The objective of this study was to determine the irritative potential of two petroleum derived operational jet fuels and four alternative fuels following a single exposure to the skin of New Zealand White rabbits. Operational fuels included two JP-8 formulations: JP-8 containing 21.25 mass percent aromatic components as a baseline control for the study and a second high aromatic (HA) JP-8 containing 28.05 mass percent aromatics for comparison with higher aromatic alternative fuels. The alternative fuels assessed were KiOR hydroprocessed depolymerized cellulosic jet (HDCJ) fuel; ReadiJet fuel produced by Applied Research Associates; Amyris C15 Direct Sugar to Hydrocarbon (DSHC); and Virent Synthetic Aromatic Kerosene (SAK). There were no significant differences in irritation noted between the baseline fuels (JP-8 and HA JP-8) and the four alternate jet fuels; all were slightly irritating when exposed under occluded and semi-occluded conditions, with the exception of ?ReadiJet? which was nonirritating when exposed semi-occluded. It is not expected that normal handling of these fuels would result in increased dermal irritation among airmen., Prepared in cooperation with, WIL Research Laboratories LLC, Ashland, OH and Univ. of Dayton Research Institute, Wright-Patterson AFB, OH.

The dermal irritation potential of ten jet fuels of interest to the U.S. Air Force was studied, including petroleum-derived JP-8. Five of the alternative fuels were synthetic paraffinic kerosenes (SPK) derived from non-petroleum fossil fuel feedstocks utilizing a Fischer-Tropsch synthesis (FT-SPK): Sasol iso-paraffinic kerosene (IPK), Sasol gas to liquid (GTL)-1 and GTL-2, Shell GTL and Syntroleum S-8 (synthetic JP-8). Four fuels were renewable bio-based fuels: Syntroleum R-8 hydroprocessed esters and fatty acids jet fuel derived from mixed fats and oils (HEFA-F), Syntroleum Sapphire derived from algae (HEFA-A), Amyris IPK and Swedish Biofuel. Each fuel was applied for four hours to the skin of New Zealand White (NZW) rabbits using occluded or semi-occluded exposures, and evaluated by the Draize method. A score of slightly irritating was determined for the occluded and semi-occluded exposures to all test substances, with the exception of a score of non-irritating for the semi-occluded exposures of Sasol IPK, SyntroleumS-8 and HEFA-F. Very slight erythema persisted through study day 14 for the occluded exposures to Amyris IPK, Swedish Biofuel, and HEFA-A. Normal handling of these fuels should not result in increased dermal irritation among airmen., Prepared in collaboration with the Henry M. Jackson Foundation for the Advancement of Military Medicine, Wright-Patterson AFB, OH, and WIL Research Laboratories LLC, Ashland, OH.

Toxicologists at 711 HPW/RHDJ have reviewed the 2013 document published by the Agency for Toxic Substances and Disease Registry (ATSDR) entitled Addendum to the Toxicological Profile for Jet Fuels (JP-5 and JP-8) (ATSDR, 2013). The full document Toxicological Profile for JP-5 and JP-8 , published in 1998 (ATSDR, 1998), is scheduled for update in FY14. A review of the Addendum identified concerns over the quality of a subset of studies summarized in the 2013 document and the potential inclusion of this subset in the 2014 update. The purpose of this special report is to provide information to supplement the FY14 update of the ATSDR Toxicological Profile for JP-5 and JP-8, and to present recommendations for data inclusion. The authors conclude that the exposure compounds and concentrations are unknown in studies published by the University of Arizona utilizing the DeVilbiss Ultra-Neb nebulizer exposure system. Therefore these studies are unsuitable for assessment of JP-8 risk. ATSDR should not handle these studies as key studies in their FY14 update., Prepared in collaboration with AFCEC/CZTE, JBSA Lackland AFB, TX. Prepared in cooperation with the Henry M. Jackson Foundation, WPAFB, OH.

The Department of Defense is actively pursuing the development of alternative fuels to augment or replace petroleum-based jet fuels. All new fuels are potentially hazardous to Air Force personnel and require toxicity evaluation. Hydroprocessed Esters and Fatty Acids jet fuel (HEFA) is a type of hydrotreated renewable jet fuel currently under consideration. One specific type of HEFA is generated from oils extracted from the camelina plant (Camelina sativa; HEFA-C). In order to evaluate potential toxicity of HEFA-C, an in vivo 90-day whole body inhalation study was performed with the fuel (concentrations of 0, 200, 700 and 2000 mg/cu m for 6 hours/day, 5 days/week) using male and female Fischer 344 rats. There was no change in food consumption attributed to fuel exposure and the average body weight was found to slightly decrease (not statistically significant) in animals exposed to the high concentration. Micronucleus test was negative for evidence of genotoxicity. No significant effects were observed for clinical chemistry or hematology analyses and no significant neurobehavioral effects were observed based on functional observational battery and motor activity tests. Minimal effects attributable to HEFA-C exposure were observed with histopathology. These effects included goblet cell hyperplasia of nasal epithelium and olfactory epithelium degeneration at the highest concentration of exposure. These two nasal cavity locations were concluded to be the primary target tissues for HEFA-C in this 90-day study; HEFA-C toxicity overall was less than the current jet fuel, JP-8., Prepared in collaboration with Henry M. Jackson Foundation for the Advancement of Military Medicine, Wright-Patterson AFB, OH and Charles River Laboratories, Pathology Associates, Frederick, MD.

The purpose of this technical report is two-fold. First, this technical report presents the results of a sensory irritation assay conducted in male Swiss-Webster mice exposed to different concentrations of hydroprocessed esters and fatty acids (HEFA) bio-based jet fuels, HEFA-Camelina (HEFA-C) and HEFA-Tallow (HEFA-T). The mice were exposed via a modified nose-only plethysmograph tube to each fuel, administered as an aerosol/vapor combination. For HEFA-C, the predicted RD50 (50 percent reduction in respiratory rate) was greater than 11,755 mg/m3. For HEFA-T, the predicted RD50 was greater than 13,306 mg/m3. This technical report also summarizes toxicity data for HEFA fuels, including HEFA-C, HEFA-T and a HEFA fuel with a feedstock of mixed animal fats and oils (HEFA-F). HEFA toxicity data are then compared with toxicity data from synthetic paraffinic kerosene (SPK) alternative jet fuel and petroleum derived JP-8. The toxicity data are used to develop a comparative occupational exposure limit (OEL) for HEFA fuels that concurs with the current JP-8 OEL (200 mg/m3)., Prepared in collaboration with the Henry M. Jackson Foundation for the Advancement of Military Medicine, Wright-Patterson AFB, OH, the Naval Medical Research Unit-Dayton, Wright-Patterson AFB, OH, and AFRL/RQTF, Wright-Patterson AFB, OH.

The U.S. Air Force is developing alternative fuels to decrease dependence on foreign oil. All new fuels are potentially hazardous to Air Force personnel and require toxicity evaluation. The objective of the dermal irritation study was to determine the irritative potential of three biobased jet fuels, Hydroprocessed Esters and Fatty Acids-Camelina (HEFA-C), HEFA-Tallow (HEFA-T) and HEFA-Animal Fats and Oils (HEFA-F), and to compare the results with the irritative potential of petroleum based JP-8. Exposures consisted of a single occluded or semi-occluded application to the skin of albino rabbits. Dermal irritation scores for all three HEFA fuels and JP-8 indicated that the fuels were slightly irritating to rabbit skin. One exposure (HEFA-F, semi-occluded) was non-irritating. The Salmonella-Escherichia coli/microsome plate incorporation assay examined two HEFA fuels, HEFA-C and HEFA-T, for mutagenic activity. HEFA-C and HEFA-T were judged to be non-mutagenic under the test conditions used in this study; therefore, the test substances were determined to be negative in the bacterial reverse mutation assay., Prepared in cooperation with SRI International, Menlo Park, CA and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Wright-Patterson AFB, OH.

Laboratory studies support the potential for jet fuel to promote noise induced hearing loss. Noise alone induces hearing loss due to loss of hair cells in the cochlea, associated with oxidative stress. Jet fuel toxicity in association with noise may be at least partially explained by increased free radical production and oxidative stress at the cellular level, resulting in hair cell dysfunction and loss. This project combines a physiologically-based pharmacokinetic (PBPK) model to describe jet fuel component concentrations in the cochlea with pharmacodynamic (PD) models of free radical formation in the cochlea by both noise and jet fuel components, and mathematical models to predict the combined impact on hair cell functionality and loss. Further development of this preliminary combined PBPK-PD model of JP-8 induced hearing loss with noise will provide the basis for estimating the potential risk to humans exposed to the same chemical and sound scenarios in occupational settings., Prepared in cooperation with the Henry M. Jackson Foundation for the Advancement of Military Medicine Wright-Patterson AFB, OH. Sponsored in part by the Air Force Medical Support Agency.

Multiple oximes have been synthesized and evaluated for use as countermeasures against chemical warfare nerve agents. The current U.S. military and civilian oxime countermeasure, 2-[(hydroxyimino)methyl]-1-methylpyridin-1-ium chloride (2-PAM), is under consideration for replacement with a more effective acetylcholinesterase reactivator, 1,1'-methylenebis{4-hydroxyiminomethyl}pyridinium dimethanesulfonate (MMB-4). Kinetic data in the scientific literature for MMB-4 are limited; therefore, a physiologically based pharmacokinetic (PBPK) model was developed for a structurally related oxime, 1,1'-trimethylenebis{4- hydroximinomethyl}pyridinium dibromide. Based on a previous model structure for the organophosphate diisopropylfluorophosphate, the model includes key sites of acetylcholinesterase inhibition (brain and diaphragm), as well as fat, kidney, liver, rapidly perfused tissues and slowly perfused tissues. All tissue compartments are diffusion limited. Model parameters were collected from the literature, predicted using quantitative structure-property relationships or, when necessary, fit to available pharmacokinetic data from the literature. The model was parameterized using rat plasma, tissue and urine time course data from intramuscular administration, as well as human blood and urine data from intravenous and intramuscular administration; sensitivity analyses were performed. The PBPK model successfully simulates rat and human data sets and has been evaluated by predicting intravenous mouse and intramuscular human data not used in the development of the model. Monte Carlo analyses were performed to quantify human population kinetic variability in the human evaluation data set. The model identifies potential pharmacokinetic differences between rodents and humans, indicated by differences in model parameters between species. The PBPK model can be used to optimize the dosing regimen to improve oxime therapeutic efficacy in a human population., Prepared in cooperation with the Henry M. Jackson Foundation for the Advancement of Military Medicine, Wright-Patterson AFB, OH.

1,4-dioxane has been used as a stability additive in a number of industrial solvents and has found its way into the environment, especially in groundwater. At current and former military installations where solvents were used, there has been growing concern for assessing the health risk involving human exposure to dioxane. Consequently, we conducted an acute inhalation study, in which we exposed male and female Fischer 344 rats for 6 hours to 0, 100, 300, 800, 2200 or 6000 ppm dioxane and assessed them at 2 days post-exposure or 2 weeks following a recovery period. We also conducted a two-week inhalation study, in which we exposed male and female rats 6 hours/day, 5 days/week to 0, 100, 1600 or 3200 ppm dioxane and assessed them at 1 day post-exposure or following the 2-week recovery period. In the acute study, two rats in the highest exposure groups had vacuolar changes in their nasal cavities two days post-exposure but they fully recovered after two weeks. In the two-week study, animals responded with numerous degenerative changes (lesions in nasal cavity, liver and kidney; hepatic single-cell necrosis). Male rats in the mid- and high concentration groups did not recover fully from hepatic single cell necrosis two weeks after exposure. The lowest observed adverse effect level (LOAEL) for 1,4-dioxane in the 2-week study is 100 ppm., PDF updated 24 Jun 2013.

FT jet fuel is a synthetic organic mixture produced using the Fischer-Tropsch (FT) process that is being developed to replace or augment petroleum-derived JP-8 jet fuel for military use by the U.S. armed forces. The FT toxicity testing program results are reviewed. The final study, sensory irritation potential in male Swiss-Webster mice, is evaluated. Groups of four mice were exposed for 30 minutes to FT jet fuel vapor/aerosol atmospheres. Group mean exposure concentrations were 2225, 6844 and 9425 mg/m3. FT jet fuel evoked breathing patterns characteristic of upper airway sensory irritation. The RD50 (50 percent respiratory rate depression) value was calculated to be 10939 mg/m3. JP-8 has an RD50 of 2,876 mg/m3. FT jet fuel is less irritating than JP-8. A health hazard assessment was conducted for FT jet fuel utilizing all of the following studies: dermal irritation test (FT vs. JP-8 vs. 50/50 blend), in vitro genotoxicity tests, acute inhalation study, short-term inhalation rangefinder study, in vivo genotoxicity test in tandem with the short-term study, 90-day inhalation toxicity study and sensory irritation assay. The sensory irritation RD50 was found to be the most sensitive endpoint. Based on the proposed use of FT jet fuel as a 50/50 blend with JP-8, an occupational exposure limit (OEL) for FT jet fuel is recommended at 200 mg/m3, in concurrence with the current JP-8 OEL of 200 mg/m3., Prepared in collaboration with USAF School of Aerosapace Medicine, Department of Occupational & Environmental Health, Risk Analysis Branch, Wright-Patterson AFB, OH; Henry M. Jackson Foundation for the Advancement of Military Medicine, Wright-Patterson AFB, OH; The Hamner Institutes for Health Sciences, Research Triangle Park, NC, and US Navy Drug Screening Laboratory, San Diego, CA.

Ammonium dinitramide (ADN) is a class 1.1 explosive oxidizer being considered for use in solid rocket propellant mixtures. Studies performed evaluating the toxicity of ADN have included an acute and subacute toxicity screen, a 90-day reproductive screen and three follow-on reproductive studies, electron paramagnetic resonance (EPR) spectroscopy studies, mutagenicity assays and a study evaluating the effects of ADN on hepatocytes in vitro. The LD50 in rats is 823 mg/kg, indicating ADN is moderately toxic. The results also indicated that ADN is a female reproductive toxicant in rats, causing implantation failure in early gestation; follow-on studies implied that ADN is embryotoxic. EPR studies indicated that ADN can decompose to form reactive nitrogen metabolites which can be harmful in biological systems. The hepatocyte studies suggested that ADN has the potential for directly affecting cellular DNA in vitro; these results are supported by traditional genotoxicity assays which reported that ADN is mutagenic.

FT or S-8 jet fuel is a synthetic organic mixture produced using the Fischer-Tropsch (FT) process that converts natural gas to liquid hydrocarbons. This study was designed to assess the potential inhalation toxicity of FT jet fuel aerosol and vapor via whole-body inhalation exposure to male and female Fischer-344 rats for 6 hours per day, 5 days per week over approximately 90 days, at concentrations of 0, 200, 700, and 2000 mg/cu m. In the motor activity test, males exposed to the highest concentration of FT jet fuel showed a reduction in total activity; the females in the same group displayed a reduction in the initial exploratory activity. Neurobehavioral function was assessed using the Functional Observation Battery (FOB). A reduction in rearing behavior was observed in females exposed at the highest concentration. Olfactory epithelial degeneration and respiratory epithelial hyperplasia was observed in the nasal airways of the high concentration male and female rats. In the lung, minimal to mild multifocal areas of inflammatory cell infiltration were observed in the high concentration groups in male and female rats. Animals exposed to the high concentration of jet fuel showed somewhat lower body weights. Differences in the average organ weights were seen between the high exposure concentration and controls in the liver, thymus, epididymides, spleen, and heart of male rats, and lungs, kidneys, and brain of females. No significant differences were observed for the andrology endpoints or the vaginal cytology results. Toxicity results were comparable to current jet fuel, JP-8., The original document contains color images.

FT (or S-8) jet fuel is a synthetic organic mixture produced using the Fischer-Tropsch (FT) process that transforms natural gas to liquid hydrocarbons. Studies are being conducted to thoroughly evaluate the toxicity of FT jet fuel. First, an acute inhalation toxicity limit test was conducted; FT jet fuel with additives was administered via inhalation exposure to rats once for 4 hours at the maximum specified concentration (2000 mg/m3). No lethality or adverse clinical signs were demonstrated. In the second study, FT jet fuel, with JP-8 additive package, was administered as an aerosol and vapor mixture via repeated inhalation exposure to rats for 6 hours per day, 5 days per week over 2 weeks at concentrations of 0, 500, 1000 and 2000 mg/m3. A slight but significant effect on bodyweight was observed in males exposed to the high (2000 mg/m3) concentration. In the nasal tissues at the intermediate (1000 mg/m3) and high (2000 mg/m3) concentrations, minimal to mild olfactory epithelial degeneration was observed, increasing with the higher concentration, and with deeper penetration into the nose. In the lung, foci of inflammatory cell infiltration were observed in all high and some intermediate concentration exposure group animals. FT jet fuel is similar to or less toxic than JP-8 in equivalent tests. In addition, micronucleus induction was tested; FT jet fuel does not induce micronuclei, indicating that the fuel is not genotoxic. A hydrocarbon fingerprint analysis of the aerosol and vapor phase of the delivered test fuel was performed.