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.     

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.     

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.     

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.     

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.     

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.     

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.     

JP-8 jet fuel exposure results in immediate immunotoxicity,which is cumulative over time

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. In the present study, the immediate effects of JP-8 exposure on the immune system were analyzed. Exposure of mice once to a single 1000 mg/m3 concentration of JP-8 for one hour resulted in significant immune organ weight loss and loss of viable immune cells from the spleen within two hours post-exposure. Although a similar exposure had no effect on thymus organ weight, it did result in significant losses of viable immune cells at one hour post-exposure. It was also observed that a loss of viable bone marrow cells could be seen at four hours post-exposure, with a return to baseline levels by 24 hours post-exposure. In terms of peripheral blood immune cells, a significant loss of viable immunecells was observed within one hour post-exposure, which became more pronounced with time. Further, it was observed that a single one-hour JP-8 exposure resulted in an immediate loss of immune function at one hour post-exposure that did not recover within 24 hours. An extension of the above experiments revealed that each additional one hour/day of exposure to 1000 mg/m3 of JP-8 promulgates the significant immunotoxicity described above. That is, spleenic organ weights, as well as viable cell numbers, continued to decline with additional days of short-term exposure. Thymic organ weights were significantly reduced at three to four days of one-hour exposures, with a continuing loss of viable cell numbers. Significantly, functional immune responses continued to deteriorate with each additional day of JP-8 exposure. Thus, low concentration JP-8 jet fuel exposures have significant effects on the immune system, these effects occur rapidly and these effects are cumulative over time.     

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.     

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.     

Correlation between urinary 2-methoxy acetic acid and exposure of 2-methoxy ethanol

OBJECTIVES: To examine the correlation between airborne 2-methoxy ethanol (ME) exposures and the urinary 2-methoxy acetic acid (MAA) and to recommend a biological exposure index (BEI) for ME. METHODS: 8 Hour time weighted average (TWA) personal breathing zone samples and urine samples before and after the shift were collected from Monday to Saturday for 27 workers exposed to ME and on Friday for 30 control workers. RESULTS: No correlation was found between airborne exposure to ME and urinary MAA for nine special operation workers due to the use of personal protective equipment. For 18 regular operation workers, a significant correlation (r = 0.702, p = 0.001) was found between urinary MAA (mg/g creatinine) on Friday at the end of the shift and the weekly mean exposures of ME in a 5 day working week. The proposed BEI, which corresponds to exposure for 5 days and 8 hours a day to 5 ppm, extrapolated from the regression equation is 40 mg MAA/g creatinine. A significant correlation was also found between the weekly increase of urinary MAA (Friday after the shift minus Monday before the shift) and the weekly mean exposures of ME (r = 0.741). The recommended value of the weekly increase of urinary MAA for 5 days repeated exposures of 5 ppm ME is 20 mg/g creatinine. No urinary MAA was detected in workers in the non-exposed control group. CONCLUSIONS: The Friday urinary MAA after the shift or the weekly increase of urinary MAA is a specific and a good biomarker of weekly exposure to ME.     

Evaluation of immunotoxicity induced by single or concurrent exposure to N,N-diethyl-m-toluamide (DEET), pyridostigmine bromide (PYR), and JP-8 jet fuel

Approximately 5,000 to 80,000 of the US service personnel involved in the Persian Gulf War have complained of a variety of nonspecific symptoms since their return in 1991. These symptoms have been collectively labeled Gulf War Illness and include muscle fatigue, general malaise, myalgia, impaired cognition, ataxia, headaches, fever, joint pain, skin rash, gastrointestinal disturbances, sleep disturbances, and respiratory difficulties. Exposures of military and service personnel were diverse and included the prescribed anti-nerve gas agent pyridostigmine bromide (PYR), N.N-diethyl-m-toluamide (DEET) insect repellent, and environmental exposures to jet fuel. Thus, studies in our laboratory were undertaken to determine if concurrent exposure to these agents, singly or in combination, would contribute to significant alterations in immunological function and disease susceptibility. To assess immune status, eight-week old B6C3F1 female mice were exposed for 14 days to single compounds or tertiary mixtures of 15.5 mg/kg DEET, 2 mg/kg PYR, and 500 mg/kg JP-8 (termed low dose), or 31 mg/kg DEET, 5 mg/kg PYR, and 1,000 mg/kg JP-8 (termed high dose). Immunosuppression was assessed 24 h after the last exposure. No remarkable alterations were evident in hematological parameters, spleen and thymus organ weight and total cellularity, natural killer (NK) cell activity, cytotoxic T-cell activity, or mitogen-induced lymphocyte proliferation after exposure to either single or tertiary mixtures at low or high doses. A few changes in CD4/CD8 flow cytometric lymphocyte subpopulations were detected after exposure to the tertiary mixture at the high dose. Delayed type hypersensitivity (DTH) was decreased by 88% after exposure to the high-dose mixture, and suppression of antibody-specific IgM immune responses (plaque-forming cell, PFC) occurred after exposure to all single and tertiary mixtures at both dose levels. In the PFC response, antagonism was apparent in the mixture, while coexposure to these agents resulted in a synergistic effect in the DTH response. Susceptibility to B16F10 tumor or Listeria monocytogenes challenge was not affected after single or tertiary exposures. These data suggest that combined exposure to DEET, PYR, and JP-8 does not profoundly alter many immunological endpoints, but does selectively target functional endpoints such as the PFC and DTH response. This should be considered when assessing human health risks in the military environment.     

Assessment of urinary trans, trans-muconic acid as a biomarker of exposure to benzene

OBJECTIVE: To assess the use of trans, trans-muconic acid as a biomarker of occupational exposure to benzene. METHODS: Trans, trans-muconic acid in urine samples of exposed (exposed group, n=36) and non-exposed (non-exposed group, n=116) workers to benzene. Urinary levels of trans, trans-muconic acid were quantified by high-performance liquid chromatography. The study sample consisted of subjects exposed to benzene in an oil refinery in Belo Horizonte, Brazil. Non-parametric statistical analysis was carried out using Kruskall-Wallis test, Mann-Whitney test and Spearman correlation at p<0.05. RESULTS: Workers were exposed on average to benzene levels of 0.15 +/- 0.05 mg/m3 (0.05 ppm) and they showed a urinary trans, trans-muconic acid mean value of 0.19 +/- 0.04 mg/g of creatinine. The reference value range of trans, trans-muconic acid in non-exposed subjects was 0.03 to 0.26 mg/g of creatinine (mean 0.10 +/- 0.08 mg/g of creatinine). There was seen a statistical difference between trans, trans-muconic acid levels in urine samples from exposed and non-exposed groups. There was no correlation between urinary trans, trans-muconic acid and air benzene levels. There was no correlation between urinary trans, trans-muconic acid levels in the exposed group and smoking. Alcohol consumption up to 48 hours before sampling procedure showed no effect on trans, trans-muconic acid levels in both exposed and non-exposed groups. There was however a correlation between age (range 18 to 25 years) and urinary metabolite levels in the latter group. CONCLUSIONS: The results show that it is important to evaluate the effect of age and smoking habits on urinary trans, trans-muconic acid levels.     

Dehydroabietic acid as a biomarker for exposure to colophony

BACKGROUND: Colophony (rosin) is a natural product derived from the resin of coniferous trees with many industrial applications including soldering fluxes. Exposure to colophony fume through soldering is one of the leading causes of occupational asthma in the UK. AIMS: To assess occupational exposure to colophony from solder fume at selected workplaces in the UK and to investigate the use of dehydroabietic acid (DHA) as a biomarker of exposure. METHODS: Six companies in the UK electronics industry were visited and occupational hygiene assessments of extent and control of exposure to rosin-based solder flux fume were undertaken. Urine samples were analysed for one of the main constituents of rosin, DHA. RESULTS: There was a positive linear relationship between airborne exposure to solder fume and urinary DHA level. The levels of urinary DHA measured in UK workers were significantly lower than those previously measured in African workers because of the use of appropriate exposure control measures, for example, local exhaust ventilation with fixed ducting and flexible hose, tip extraction, etc. It is suggested that good occupational hygiene practice would result in urinary DHA levels of <3 micromol/mol creatinine in a post-shift urine sample. CONCLUSIONS: Urinary DHA is a valid biomarker of exposure to colophony in solder fume. Further work on the excretion kinetics of urinary DHA, the possibility of skin absorption and further occupational hygiene surveys would be beneficial.     

Allylmercapturic acid as urinary biomarker of human exposure to allyl chloride.

OBJECTIVE: To evaluate the use of urinary mercapturic acids as a biomarker of human exposure to allyl chloride (3-chloropropene) (AC). During three regular shut down periods in a production factory for AC, both types of variables were measured in 136 workers involved in maintenance operations. METHODS: Potential airborne exposure to AC was measured by personal air monitoring in the breathing zone. In total 205 workshifts were evaluated. During 99 workshifts no respiratory protection equipment was used. Mercapturic acid metabolites were measured in urinary extracts by gas chromatography-mass spectrometry (GC-MS). RESULTS: During 86 work shifts when no respiratory protection was used the air concentrations of AC were below the Dutch eight hour time weighted average (8 h-TWA) occupational exposure limit (OEL) of AC (3 mg/m3), whereas in 13 workshifts the potential exposure, as measured by personal air monitoring, exceeded the OEL (3.3 to 17 mg/m3). With the aid of GC-MS, 3-hydroxypropylmercapturic acid (HPMA) was identified as a minor and allylmercapturic acid (ALMA) as a major metabolite of AC in urine samples from the maintenance workers exposed to AC. The concentrations of ALMA excreted were in a range from < 25 micrograms/l (detection limit) to 3550 micrograms/l. The increases in urinary ALMA concentrations during the workshifts correlated well with the 8h-TWA air concentrations of AC (r = 0.816, P = 0.0001, n = 39). Based on this correlation, for AC a biological exposure index (BEI) of 352 micrograms ALMA/g creatinine during an eight hour workshift is proposed. In some urine samples unexpectedly high concentrations of ALMA were found. Some of these could definitely be attributed to dermal exposure to AC. In other cases garlic consumption was identified as a confounding factor. CONCLUSION: The mercapturic acid ALMA was identified in urine of workers occupationally exposed to airborne AC and the increase in ALMA concentrations in urine during a workshift correlated well with the 8 h-TWA exposure to AC. Garlic consumption, but not smoking, is a potential confounding factor for this biomarker of human exposure to AC.     

Validation of urinary trichloroacetic acid as a biomarker of exposure to drinking water disinfection by-products

Disinfection by-products (DBPs) in drinking water represent a public health issue and a challenge for epidemiology to provide evidence towards the causation of various hypothesized health effects. Validation of a biomarker of exposure to DBPs is a strategy to achieve progress which has been advocated. The objective of this study was to validate urinary trichloroacetic acid (TCAA) excretion as a biomarker of exposure to DBPs in an experimental exposure cohort. A total of 52 healthy women participated in the study. Participants consumed supplied tap water for 15 d and provided urine and blood samples for TCAA measurements. The findings revealed that (1) background levels of TCAA in urine and blood were readily detectable, (2) TCAA levels in blood and urine increased with increased amounts of TCAA ingested, (3) the correlations between measurements of TCAA ingestion and urinary excretion were modest (r=0.66, p<0.001) based on one days' sampling and high (r=0.77–0.83, p<0.001) based on two to four days' sampling, (4) the correlations between measurements of TCAA ingestion and blood TCAA concentration were high (r=0.80, p<0.001) and (5) multiple days' urinary TCAA measures improved the prediction of TCAA ingestion through urinary TCAA excretion. TCAA can be a valid biomarker of exposure for DBPs in drinking water.     

Analysis of urinary N-acetyl-S-(propionamide)-cysteine as a biomarker for the assessment of acrylamide exposure in smokers

Acrylamide, classified by the IARC as a probable human carcinogen (Group 2A), is present in cigarette mainstream smoke and also some high-temperature-processed foods, thus smokers and consumers of certain foods are at risk of acrylamide exposure. The objectives of this study were to analyze N-acetyl-S-(propionamide)-cysteine (NASPC), an acrylamide metabolite, in the urine of smokers and nonsmokers, and to investigate the association between acrylamide exposure and urinary NASPC levels in smokers and nonsmokers in order to validate NASPC as a biomarker for the assessment of acrylamide exposure. Urine samples from 63 male military officers were collected as well as background personal information and smoking habits using questionnaires. Acrylamide exposure from tobacco smoke was represented by self-reported daily cigarette consumption and urinary cotinine levels. NASPC and cotinine were analyzed using our newly developed liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) methods. Our results reveal a statistically significant linear relationship between urinary NASPC and cotinine levels for smokers (Spearman correlation coefficient r=0.402, P=0.028), but insignificantly so for nonsmokers. These results verify our suggestion that urinary NASPC could serve as a sensitive, specific, noninvasive, and easily accessible biomarker for low-dose acrylamide exposure as also exposure to carcinogens in tobacco smoke. Routine monitoring of urinary NASPC could be used to assess human exposures to acrylamide in the living environment and the workplace.     

Effects of aerosol-vapor JP-8 jet fuel on the functional observational battery, and learning and memory in the rat

To determine whether JP-8 jet fuel affects parameters of the Functional Observational Battery (FOB), visual discrimination, or spatial learning and memory, the authors exposed groups of male Fischer Brown Norway hybrid rats for 28 d to aerosol/vapor-delivered JP-8, or to JP-8 followed by 15 min of aerosolized substance P analogue, or to sham-confined fresh room air. Behavioral testing was accomplished with the U.S. Environmental Protection Agency's Functional Observational Battery. The authors used the Morris swim task to test visual and spatial learning and memory testing. The spatial test included examination of memory for the original target location following 15 d of JP-8 exposure, as well as a 3-d new target location learning paradigm implemented the day that followed the final day of exposure. Only JP-8 exposed animals had significant weight loss by the 2nd week of exposure compared with JP-8 with substance P and control rats; this finding compares with those of prior studies of JP-8 jet fuel. Rats exposed to JP-8 with or without substance P exhibited significantly greater rearing and less grooming behavior over time than did controls during Functional Observational Battery open-field testing. Exposed rats also swam significantly faster than controls during the new target location training and testing, thus supporting the increased activity noted during Functional Observational Battery testing. There were no significant differences between the exposed and control groups' performances during acquisition, retention, or learning of the new platform location in either the visual discrimination or spatial version of the Morris swim task. The data suggest that although visual discrimination and spatial learning and memory were not disrupted by JP-8 exposure, arousal indices and activity measures were distinctly different in these animals.     

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.