Estimating dermal exposure to jet fuel (naphthalene) using adhesive tape strip samples

A simple, non-invasive dermal sampling technique was developed and tested on 22 human volunteers under laboratory conditions to estimate acute dermal exposure to jet fuel (JP-8). Two sites on the ventral surface of each forearm were exposed to 25 micro l of JP-8 and the non-viable epidermis (stratum corneum) was sequentially tape-stripped using an adhesive tape. Samples were extracted with acetone and analyzed by gas chromatography/mass spectrometry. Analysis of the first tape strips indicated that JP-8 was rapidly removed from the stratum corneum over the 20 min study period. On average, after 5 min of exposure the first two tape strips removed 69.8% of the applied dose. The amount recovered with two tape strips decreased over time to a recovery of 0.9% 20 min after exposure. By fitting a mixed-effects linear regression model to the tape strip data, we were able to estimate accurately the amount of JP-8 initially applied. This study indicates that naphthalene has a short retention time in the human stratum corneum and that the tape stripping method, if used within 20 min of the initial exposure, can be used to measure reliably the amount of naphthalene initially in the stratum corneum due to a single exposure to jet fuel. We are currently investigating the applicability of the developed mixed-effects linear regression model to estimate acute JP-8 exposure levels based upon naphthalene measurements from tape strips collected from occupationally exposed workers.     

Dermal exposure to jet fuel (JP-8) in US Air Force personnel

Limited research has been conducted on dermal exposure and risk assessment, owing to the lack of reliable measurement techniques and data for quantitative risk assessment. We investigated the magnitude of dermal exposure to jet propulsion fuel 8 (JP-8), using naphthalene as a surrogate, on the US Air Force fuel-cell maintenance workers. Dermal exposure of 124 workers routinely working with JP-8 was measured using a non-invasive tape-strip technique coupled with gas chromatography-mass spectrometry analysis. The contribution of job-related factors to dermal exposure was determined using multiple linear regression analyses. Average whole body dermal exposure to naphthalene (as a marker for JP-8) was 7.61 +/- 2.27 ln(ng m(-2)). Significant difference (P < 0.0001) between the high-exposure group [8.34 +/- 2.23 ln(ng m(-2))] and medium- and low-exposure groups [6.18 +/- 1.35 ln(ng m(-2)) and 5.84 +/- 1.34 ln(ng m(-2)), respectively] was observed reflecting the actual exposure scenarios. Skin irritation, use of booties, working inside the fuel tank and the duration of JP-8 exposure were significant factors explaining the whole body dermal exposure. This study clearly demonstrates the efficiency and suitability of the tape-strip technique for the assessment of dermal exposure to JP-8 and that naphthalene can serve as a useful marker of exposure and uptake of JP-8 and its components. It also showed that the skin provides a significant route for JP-8 exposure and that actions to reduce exposure are required. Studies to investigate the relative contribution of dermal uptake of JP-8 on total body dose and the toxicokinetics of dermal exposure to JP-8 are underway.     

Dermal exposure to jet fuel JP-8 significantly contributes to the production of urinary naphthols in fuel-cell maintenance workers

Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure.     

PBTK modeling demonstrates contribution of dermal and inhalation exposure components to end-exhaled breath concentrations of naphthalene

BACKGROUND: Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. OBJECTIVE: Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. METHODS: The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. RESULTS: The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 x 10(-5) cm/hr, b) permeability coefficient for the viable epidermis 3.0 x 10(-3) cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers' exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). CONCLUSIONS: PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures.     

Urinary biomarkers of exposure to jet fuel (JP-8)

Benzene, naphthalene, and 1- and 2-naphthol were measured in urine samples obtained from 322 U.S. Air Force personnel categorized a priori as likely to have low, moderate, or high exposure to jet fuel [jet propulsion fuel-8 (JP-8)]. In postexposure samples, levels of these analytes in the high-exposure group were 3- to 29-fold greater than in the low-exposure group and 2- to 12-fold greater than in the moderate-exposure group. Heavy exposure to JP-8 contributed roughly the same amount of benzene and more than three times the amount of naphthalene compared with cigarette smoking. Strong correlations were observed among postexposure levels of naphthalene-based biomarkers in urine and naphthalene in air and breath. We conclude that urinary naphthalene and the naphthols can serve as biomarkers of exposure to jet fuel. Of these, the naphthols are probably more useful because of their greater abundance and slower elimination kinetics.     

Tape-strip sampling for measuring dermal exposure to 1,6-hexamethylene diisocyanate

OBJECTIVES: This study describes the development and evaluation of a method for sampling layers of the stratum corneum for the quantitation of dermal exposure to 1,6-hexamethylene diisocyanate (HDI). METHODS: HDI deposited on skin was collected by the removal of stratum corneum with adhesive tape, derivatized with 1-(2-methoxyphenyl)piperazine, and quantitated as the urea derivative (HDIU) by liquid chromatography-mass spectrometry (LC-MS). This LC-MS method was tested by analyzing tape spiked with HDI-containing products, then applied to tape samples collected from the skin of an auto-body shop worker exposed to polyurethane paint aerosols. RESULTS: The limits of detection and quantitation were 20 and 50 fmol per injection, respectively. The recovery of HDI from the tape was 99.3% [95% confidence interval (95% CI) 97.1-102]. HDIU was stable at -40 degrees C, degrading by 0.28% (95% CI 0.10-0.46) per day. Quantifiable amounts of HDI were observed in 42.6% of the first three successive tape-strip samples collected from 36 different sites on the skin of the worker. The amount of HDI recovered from the collection sites on skin, measured by summing the levels collected with three successive tape-strips, ranged from nondetectable to 1874 pmol. CONCLUSIONS: This study demonstrates that HDI on skin can be collected with tape-strips and quantified at occupational levels using LC-MS.     

Benzene and naphthalene in air and breath as indicators of exposure to jet fuel

Aims: To estimate exposures to benzene and naphthalene among military personnel working with jet fuel (JP-8) and to determine whether naphthalene might serve as a surrogate for JP-8 in studies of health effects.

Methods: Benzene and naphthalene were measured in air and breath of 326 personnel in the US Air Force, who had been assigned a priori into low, moderate, and high exposure categories for JP-8.

Results: Median air concentrations for persons in the low, moderate, and high exposure categories were 3.1, 7.4, and 252 µg benzene/m³ air, 4.6, 9.0, and 11.4 µg benzene/m³ breath, 1.9, 10.3, and 485 µg naphthalene/m³ air, and 0.73, 0.93, and 1.83 µg naphthalene/m³ breath, respectively. In the moderate and high exposure categories, 5% and 15% of the benzene air concentrations, respectively, were above the 2002 threshold limit value (TLV) of 1.6 mg/m³. Multiple regression analyses of air and breath levels revealed prominent background sources of benzene exposure, including cigarette smoke. However, naphthalene exposure was not unduly influenced by sources other than JP-8. Among heavily exposed workers, dermal contact with JP-8 contributed to air and breath concentrations along with several physical and environmental factors.

Conclusions: Personnel having regular contact with JP-8 are occasionally exposed to benzene at levels above the current TLV. Among heavily exposed workers, uptake of JP-8 components occurs via both inhalation and dermal contact. Naphthalene in air and breath can serve as useful measures of exposure to JP-8 and uptake of fuel components in the body.

     

Age-related differences in pulmonary inflammatory responses to JP-8 jet fuel aerosol inhalation

Our previous studies have demonstrated that JP-8 jet fuel aerosol inhalation induced lung injury and dysfunction. To further examine JP-8 jet fuel-induced inflammatory mechanisms, a total of 40 male C57BL/6 mice (young, 3.5 months; adult, 12 months; half in each age group) were randomly assigned to the exposure or control groups. Mice were nose-only exposed to room air or atmospheres of 1000 mg/m3 JP-8 jet fuel for 1 h/day for 7 days. Lung injury was assessed by pulmonary mechanics, respiratory permeability, lavaged cell profile, and chemical mediators in bronchoalveolar lavage fluid (BALF). The young and adult mice exposed to JP-8 jet fuel had similar values with regards to increased lung dynamic compliance, lung permeability, BALF cell count, and decreased PGE2. However, there were several different responses between the young-versus-adult mice with respect to BALF cell differential, TNF-alpha, and 8-iso-PGF2,, levels after exposure to JP-8 jet fuel. These data suggest that JP-8 jet fuel may have different inflammatory mechanisms leading to lung injury and dysfunction in the younger-versus-adult mice.     

Effects of in utero JP-8 jet fuel exposure on the immune systems of pregnant and newborn mice

The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Previous work has reported that JP-8 exposure is immunosuppressive. In the present study, the effects of in-utero JP-8 jet fuel exposure in mice were examined to ascertain any potential effects of jet fuel exposure on female personnel and their offspring. Exposure by the aerosol route (at 1000 mg/m3 for 1 h/day; similar to exposures incurred by flight line personnel) commencing during the first (d7 to birth) or last (d15 to birth) trimester of pregnancy was analyzed. It was observed that even 6-8 weeks after the last jet fuel exposure that the immune system of the dams (mother of newborn mice) was affected (in accordance with previous reports on normal mice). That is, thymus organ weights and viable cell numbers were decreased, and immune function was depressed. A decrease in viable male offspring was found, notably more pronounced when exposure started during the first trimester of pregnancy. Regardless of when jet fuel exposure started, all newborn mice (at 6-8 weeks after birth) reported significant immunosuppression. That is, newborn pups displayed decreased immune organ weights, decreased viable immune cell numbers and suppressed immune function. When the data were analyzed in relation to the respective mothers of the pups the data were more pronounced. Although all jet fuel-exposed pups were immunosuppressed as compared with control pups, male offspring were more affected by jet fuel exposure than female pups. Furthermore, the immune function of the newborn mice was directly correlated to the immune function of their respective mothers. That is, mothers showing the lowest immune function after JP-8 exposure gave birth to pups displaying the greatest effects of jet fuel exposure on immune function. Mothers who showed the highest levels of immune function after in-utero JP-8 exposure gave birth to pups displaying levels of immune function similar to controls animals that had the lowest levels of immune function. These data indicated that a genetic component might be involved in determining immune responses after jet fuel exposure. Overall, the data showed that in-utero JP-8 jet fuel exposure had long-term detrimental effects on newborn mice, particularly on the viability and immune competence of male offspring.     

Effects of short-term JP-8 jet fuel exposure on cell-mediated immunity

The U.S. Air Force has implemented 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 environmental toxicants such as JP-8 may have significant effects on host physiology. Jet fuel exposure has been shown to cause human liver dysfunction, abnormal electroencephalograms, shortened attention spans, and decreased sensorimotor speed. Previous studies 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 of immune function that persisted for extended periods of time (i.e., up to 4 weeks post-exposure). In the current study, an in-depth analysis of the effects of JP-8 exposure on cellular immunity was performed. Short-term (7 days, 1 h/day), low-concentration (1000 mg/m3) exposures were conducted in mice, and T cell and natural killer (NK) cell functions were analyzed 24 h after the last exposure. The exposure regimen was found to almost completely ablate NK cell function, as well as significantly suppress the generation of lymphokine-activated killer (LAK) cell activity. Furthermore, JP-8 exposure suppressed the generation of cytotoxic T lymphocyte (CTL) cells from precursor T cells, and inhibited helper T cell activity. These findings demonstrate that JP-8 jet fuel exposure has significant detrimental effects on immune functions of exposed individuals. JP-8 jet fuel should be considered a potential and significant immunotoxicant. Chronic exposure to JP-8 may have serious implications to the long-term health of exposed individuals.     

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.     

Uptake of chloroform by skin on brief exposures to the neat liquid

The uptake of chloroform into hairless rat's stratum corneum after application of the neat solvent directly to the skin has been studied. Tape stripping was used to determine amounts deposited within the stratum corneum and also the clearance of the compound from the skin following varied levels of exposure. Three minutes exposure to neat chloroform was adequate to achieve a limiting accumulation in the stratum corneum and thus it appears to take this long for the gradient of chloroform to be established fully across this structure. There was indication of progressively deeper penetration of chloroform as the exposure time was increased from 1 to 8 minutes. Local irritation and a loosening of the superficial layers of stratum corneum were apparent with as little as 2 minutes of exposure to the solvent and were exacerbated with further increases in exposure duration. Following exposure, clearance of the solvent from the skin surface was rapid. Interestingly, the rate of clearance, as followed by stripping, was comparable on live and freshly euthanized rats. This implies that once the exposure is terminated evaporation from the surface, and not systemic uptake by way of the local vasculature, is the predominant means of clearance at an open surface.     

JP-8 jet fuel exposure rapidly induces high levels of IL-10 and PGE2 secretion and is correlated with loss of immune function

The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Previous work has demonstrated that JP-8 exposure is immunosuppressive. In the present study, the potential mechanisms for the effects of JP-8 exposure on the immune system were investigated. Exposure of mice to JP-8 for 1 h/day resulted in immediate secretion of two immunosuppressive agents; namely, interleukin-10 (IL-10) and prostaglandin E2 (PGE2). JP-8 exposure rapidly induced a persistently high level of serum IL-10 and PGE2 at an exposure concentration of 1000 mg/m3. IL-10 levels peaked at 2 h post-JP-8 exposure and then stabilized at significantly elevated serum levels, while PGE2 levels peaked after 2-3 days of exposure and then stabilized. Elevated IL-10 and PGE2 levels may at least partially explain the effects of JP-8 exposure on immune function. Elevated IL-10 and PGE2 levels, however, cannot explain all of the effects due to JP-8 exposure (e.g., decreased organ weights and decreased viable immune cells), as treatment with a PGE2 inhibitor did not completely reverse the immunosuppressive effects of jet fuel exposure. Thus, low concentration JP-8 jet fuel exposures have significant effects on the immune system, which can be partially explained by the secretion of immunosuppressive modulators, which are cumulative over time.     

Substance P as prophylaxis for JP-8 jet fuel-induced immunotoxicity.

Previous studies have shown that short-term, low-concentration JP-8 exposure had significant effects on the immune system that persisted for extended periods of time. It was found that administration of aerosolized substance P (SP) was able to protect exposed animals from JP-8-induced immune changes, whereas administration of SP antagonists compounded the deleterious effects ofjet fuel exposure. Thus, SP administration appears to be a relatively simple and efficient means to reverse the immunotoxicity due to hydrocarbon exposure. In the current study, aerosolized SP was analyzed for its potential prophylactic ability to counteract JP-8-induced immunotoxicity. It was observed that concentrations as low as 1 nM were effective in ameliorating the effects of JP-8 exposure on the immune system. SP administered before JP-8 exposure could prophylactically protect both the spleen and thymus from significant organ weight loss, but could not completely restore immune cell numbers to normal, baseline levels. Furthermore, SP treatment could be delayed as long as 1 h postexposure and reverse the effects of jet fuel exposure on immune organ weight loss and immune cell recovery. Significantly, SP could be given 15 min pre-JP-8 exposure but neither 1 nor 6 h pre-JP-8 exposure, and prevent immune dysfunction as measured in mitogenesis assays. However, SP could be delayed up to 6 h post-JP-8 exposure and still almost completely restore immune function. Thus, SP appears able to both prevent and reverse the immunotoxicological effects associated with JP-8 exposure. These results also provide insight into the manner in which JP-8 jet fuel mediates its effects on the immune system.     

A tape-stripping method for measuring dermal exposure to multifunctional acrylates

Current methods for measuring dermal exposure to skin irritants and allergens, such as acrylates, have significant drawbacks for exposure assessment. A noninvasive sampling method has been developed and tested for measuring dermal exposure to a multifunctional acrylate employing a tape stripping of the nonviable epidermis (stratum corneum). Samples were subsequently extracted and a gas chromatographic method was employed for quantitative analysis of tripropylene glycol diacrylate (TPGDA). This method was tested in 10 human volunteers exposed to an a priori determined amount of TPGDA or a UV-radiation curable acrylate coating containing TPGDA (UV-resin) at different sites on hands and arms. On the average, the first tape stripping removed 94% (coefficient of variation 16%) of the theoretical quantity of deposited TPGDA and 89% (coefficient of variation 15%) of the theoretical quantity of deposited TPGDA in UV-resin 30min after exposure. Quantities of TPGDA recovered from two consecutive tape strippings accounted for all of the test agent, demonstrating both the efficiency of the method to measure dermal exposure and the potential to determine the rate of absorption with successive samples over time. In general, the amount removed by the first stripping was greater for TPGDA than for UV-resin while the second stripping removed approximately 6 and 21% of TPGDA and UV-resin, respectively. However, when the amounts removed with the first tape stripping for TPGDA or UV-resin from the five different individual sites were compared, no significant differences were observed (P=0.111 and 0.893, respectively). No significant difference was observed in recovery between TPGDA and UV-resin for the first tape stripping when calculated as a percentage of the theoretical amount (P=0.262). The results indicate that this tape-stripping technique can be used to quantify dermal exposure to multifunctional acrylates.     

The influence of hydrocarbon composition and exposure conditions on jet fuel-induced immunotoxicity

Chronic jet fuel exposure could be detrimental to the health and well-being of exposed personnel, adversely affect their work performance and predispose these individuals to increased incidences of infectious disease, cancer and autoimmune disorders. Short-term (7 day) JP-8 jet fuel exposure has been shown to cause lung injury and immune dysfunction. Physiological alterations can be influenced not only by jet fuel exposure concentration (absolute amount), but also are dependent on the type of exposure (aerosol versus vapor) and the composition of the jet fuel (hydrocarbon composition). In the current study, these variables were examined with relation to effects of jet fuel exposure on immune function. It was discovered that real-time, in-line monitoring of jet fuel exposure resulted in aerosol exposure concentrations that were approximately one-eighth the concentration of previously reported exposure systems. Further, the effects of a synthetic jet fuel designed to eliminate polycyclic aromatic hydrocarbons were also examined. Both of these changes in exposure reduced but did not eliminate the deleterious effects on the immune system of exposed mice.     

JP-8 jet fuel exposure potentiates tumor development in two experimental model systems

The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Previous work has reported that JP-8 exposure is immunosuppressive. Exposure of mice to JP-8 for 1 h/day resulted in immediate secretion of two immunosuppressive agents; namely, interleukin-10 (IL-10) and prostaglandin E2 (PGE2). Thus, it was of interest to determine if jet fuel exposure might promote tumor growth and metastasis. The syngeneic B16 tumor model was used for these studies. Animals were injected intravenously with tumor cells, and lung colonies were enumerated. Animals were also examined for metastatic spread of the tumor. Mice were either exposed to 1000 mg/m3 JP-8 (1 h/ day) for 7 days before tumor injection or were exposed to JP-8 at the time of tumor injection. All animals were killed 17 days after tumor injection. In the present study, JP8 exposure potentiated the growth and metastases of B16 tumors in an animal model. Exposure of mice to JP-8 for 1 h/day before tumor induction resulted in an approximately 8.7-fold increase in tumors, whereas those mice exposed to JP8 at the time of tumor induction had a 5.6-fold increase in tumor numbers. Thus, low concentration JP-8 jet fuel exposures have significant immune suppressive effects on the immune system that can result in increased tumor formation and metastases. We have now extended the observations to an experimental subcutaneous tumor model. JP8 exposure at the time of tumor induction in this model did not affect the growth of the tumor. However, JP8-exposed, tumor-bearing animals died at an accelerated rate as compared with air-exposed, tumor-bearing mice.     

Urinary biomarkers of occupational jet fuel exposure among Air Force personnel

There is a potential for widespread occupational exposure to jet fuel among military and civilian personnel. Urinary metabolites of naphthalene have been suggested for use as short-term biomarkers of exposure to jet fuel (jet propulsion fuel 8 (JP8)). In this study, urinary biomarkers of JP8 were evaluated among US Air Force personnel. Personnel (n=24) were divided a priori into high, moderate, and low exposure groups. Pre- and post-shift urine samples were collected from each worker over three workdays and analyzed for metabolites of naphthalene (1- and 2-naphthol). Questionnaires and breathing-zone naphthalene samples were collected from each worker during the same workdays. Linear mixed-effects models were used to evaluate the exposure data. Post-shift levels of 1- and 2-naphthol varied significantly by a priori exposure group (levels in high group>moderate group>low group), and breathing-zone naphthalene was a significant predictor of post-shift levels of 1- and 2-naphthol, indicating that for every unit increase in breathing-zone naphthalene, there was an increase in naphthol levels. These results indicate that post-shift levels of urinary 1- and 2-naphthol reflect JP8 exposure during the work-shift and may be useful surrogates of JP8 exposure. Among the high exposed workers, significant job-related predictors of post-shift levels of 1- and 2-naphthol included entering the fuel tank, repairing leaks, direct skin contact with JP8, and not wearing gloves during the work-shift. The job-related predictors of 1- and 2-naphthol emphasize the importance of reducing inhalation and dermal exposure through the use of personal protective equipment while working in an environment with JP8.     

Dose-dependent production of urinary naphthols among workers exposed to jet fuel (JP-8)

BACKGROUND: Jet propulsion fuel-8 (JP-8) is one of the largest sources of chemical exposures among Air Force personnel. Urinary naphthols have been suggested as useful biomarkers of exposure to JP-8. METHODS: Multivariate linear regression models were applied to evaluate the effects of environmental and work-related factors upon production of urinary naphthols among 323 Air Force personnel. RESULTS: Naphthalene exposure, smoking status, and their interaction, plus self-reported skin irritation explained about two-thirds of the variation in naphthol levels. The exposure-smoking interaction was consistent with induction by smoking of one or more steps in the metabolism of naphthalene and naphthalene-1,2-oxide (NapO). A supralinear dose-response relationship was observed between urinary naphthols and naphthalene exposure. CONCLUSIONS: Urinary naphthols were associated with specific sources of exposure to JP-8, arising from both inhalation and dermal contact. Smokers and nonsmokers metabolized naphthalene at different rates, consistent with induction of at least two metabolic pathways by smoking.     

Identification of target genes responsive to JP-8 exposure in the rat central nervous system

Concern for the health risk associated with occupational exposure to jet fuel has emerged in the Department of Defense. Jet propulsion fuel-8 (JP-8) is the fuel used in most US and North Atlantic Treaty Organization (NATO) jet aircraft, and will be the predominant fuel both for military land vehicles and aircraft into the twenty-first century. JP-8 exhibits reduced volatility and lower benzene content as compared to JP-4, the predominant military aircraft fuel before 1992, possibly suggesting greater occupational exposure safety. However, the higher rates of occupational exposure through fueling and maintenance of increasingly larger numbers of aircraft/vehicles raise concerns with respect to toxicity. Clinical studies of workers experiencing long-term exposure to certain jet fuels demonstrated deficits in CNS function, including fatigue, neurobehavioral changes, psychiatric disorders, and abnormal electroencephalogram (EEG). In the present study, cDNA nylon arrays (Atlas Rat 1.2 Array, Clontech Laboratories, Palo Alto, CA) were utilized to measure changes in gene expression in whole brain tissue of rats exposed repeatedly to JP-8, under conditions that simulated possible real-world occupational exposure (6 h/day for 91 days) to JP-8 vapor at 1,000 mg/m3. Gene expression analysis of the exposure group compared to the control group revealed a modulation of several genes, including glutathione S-transferase Yb2 subunit (GST Yb2); cytochrome P450 IIIAl (CYP3A1); glucose-dependent insulinotropic peptide (GIP); alpha1-proteinase inhibitor (alpha1-AT); polyubiquitin; GABA transporter 3 (GAT-3); and plasma membrane Ca2+-transporting ATPase (brain isoform 2) (PMCA2). The implications of these vapor-induced changes in gene expression are discussed.