Proteomic analysis of simulated occupational jet fuel exposure in the lung

Witzmann, Frank A.; Bauer, Mark D.; Fieno, Angela M.; Grant, Raymond A.; Keough, T.; Kornguth, Steven; Lacey, Martin P.; Siegel, Frank L.; Sun, Yiping; Wright, Lynda S.; Young, Renée; Witten, Mark L.

doi:10.1002/(sici)1522-2683(19991201)20:18<3659::aid-elps3659>3.0.co;2-m

Cited by 38 publications

(9 citation statements)

References 46 publications

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“…This is not to say that jet fuel inhalation is without consequence in the lung. Indeed, Witzmann, Witten, and their colleagues have demonstrated alterations in lung protein expression following repeated daily exposures to JP-8 (e.g., Witzmann et al, 1999;Robledo et al, 2000;Drake et al, 2003). However, in the current study no evidence could be identified that might point to a role of glutathione depletion as part of an oxidative injury involved in lung toxicity as proposed by Bulares et al (2002).…”

Section: Discussioncontrasting

confidence: 44%

Depletion of Liver Glutathione Levels in Rats: A Potential Confound of Nose-Only Inhalation

Fechter

Nelson-Miller

Gearhart

2008

Inhalation Toxicology

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Nose-only inhalation exposure chambers offer key advantages to whole-body systems, particularly when aerosol or mixed aerosol-vapor exposures are used. Specifically, nose-only chambers provide enhanced control over the route of exposure and dose by minimizing the deposition of particles either on the subjects skin/fur or on surfaces of a whole-body exposure system. In the current series of experiments, liver, brain, and lung total glutathione (GSH) levels were assessed following either nose-only or whole-body exposures to either jet fuel or to clean, filtered air. The data were compared to untreated control subjects. Acute nose-only inhalation exposures of rats resulted in a significant depletion of liver GSH levels both in subjects that were exposed to clean, filtered air as well as those exposed to JP-8 jet fuel and to a synthetic jet fuel. Glutathione levels were not altered in lung or brain tissue. Whole-body inhalation exposure had no effect on GSH levels in any tissue for any of the treatment groups. A second experiment demonstrated that the loss of GSH did not occur if rats were anaesthetized prior to and during nose-only exposure to clean, filtered air or to mixed hydrocarbons. These data appear to be consistent with studies demonstrating depletion in liver GSH levels among rats subjected to restraint stress. Finally, the depletion of GSH that was observed in liver following a single acute exposure was reduced following five daily exposures to clean, filtered air, suggesting the possibility of habituation to restraint in the nose-only exposure chamber. The finding that placement in a nose-only exposure chamber per se yields liver GSH depletion raises the possibility of an interaction between this mode of toxicant exposure and the toxicological effects of certain inhaled test substances.Nose-only inhalation exposure chambers provide toxicologists with a convenient means of exposing laboratory animals to investigational compounds while minimizing the deposition of such compounds on the subjects' skin or fur from which it might be ingested. Nose-only exposure, then, is particularly useful when test compounds contain significant aerosol components and when the investigator either seeks to determine the effect of the test compound specifically on the lungs and conducting airways or wishes to model deposition of compounds in these airways.This investigation stems from the observation that nose-only inhalation exposure to JP-8 jet fuel yielded a significant deple-

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Section: Discussioncontrasting

confidence: 44%

Depletion of Liver Glutathione Levels in Rats: A Potential Confound of Nose-Only Inhalation

Fechter

Nelson-Miller

Gearhart

2008

Inhalation Toxicology

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“…Because jet fuel vapors and aerosol are mainly an inhalational hazard, the major route of jet fuel exposure to flight and ground crew personnel is via the respiratory tract. Previous studies on JP-8 pulmotoxicology have found significant physiological (Hays et al 1995; Robledo et al 1999b; Wong et al 2004), cellular (Robledo et al 1999a), and biochemical changes (Espinoza et al 2006; Witzmann et al 1999) resulting from jet fuel exposure. Changes in airways were characterized by loss of epithelial barrier integrity and alterations of ventilatory function in bronchial and bronchiolar airways (Hays et al 1995; Robledo et al 1999a; Wang et al 2001).…”

Section: Introductionmentioning

confidence: 96%

In vivo comparison of epithelial responses for S-8 versus JP-8 jet fuels below permissible exposure limit

Wong¹,

Vargas²,

Thomas³

et al. 2008

Toxicology

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This study was designed to characterize and compare the pulmonary effects in distal lung from a low-level exposure to jet propellant-8 fuel (JP-8) and a new synthetic-8 fuel (S-8). It is hypothesized that both fuels have different airway epithelial deposition and responses. Consequently, male C57BL/6 mice were nose-only exposed to S-8 and JP-8 at average concentrations of 53 mg/m3 for 1 hour/day for 7 days. A pulmonary function test performed 24 hr after the final exposure indicated that there was a significant increase in expiratory lung resistance in the S-8 mice, whereas JP-8 mice had significant increases in both inspiratory and expiratory lung resistance compared to control values. Neither significant S-8 nor JP-8 respiratory permeability changes were observed compared to controls, suggesting no loss of epithelial barrier integrity. Morphological examination and morphometric analysis of airway tissue demonstrated that both fuels showed different patterns of targeted epithelial cells: bronchioles in S-8 and alveoli/terminal bronchioles in JP-8. Collectively, our data suggest that both fuels may have partially different deposition patterns, which may possibly contribute to specific different adverse effects in lung ventilatory function.

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“…Additionally, it is thought that alpha-2-mu is responsible for transporting low-molecular-weight hydrophobic molecules (Swenberg et al, 1989), with limited evidence that cleavage products of alpha-2-mu may be capable of transporting toxicants such as lead (Fowler & DuVal, 1991), possibly related to their cellular toxicity in the brain. Witzmann et al (1999) showed that exposure of mice to 2500 mg/m 3 JP-8 aerosol for 1 h/d for 7 d resulted in impaired protein synthesis in the lung, predicting ultrastructural damage, reduced CO 2 exchange capacity, protein charge modifications, and alterations of lung toxic/metabolic stress and detoxification systems. These fuel-induced changes can, of course, result indirectly in neurological deficits as a function of hypoxia, increased lung permeability to respiratory toxicants, or reduced capacity of the lung to metabolize potential toxicants.…”

Section: Neurological Consequences As Secondary Toxicity Effectsmentioning

confidence: 99%

“…These changes typically involve acute or persisting modulation of CNS DA, 5-HT, and/or NA neurotransmitter systems and/or of the hypothalamo-pituitary axis, and may be accompanied by subtle changes in neurobehavioral capacity. Recently published research (Nordholm, 1998;Witzmann et al, 1999;Nordholm et al, 1999; indicate that repeated exposure of rats to human "real-world" concentrations of JP-4, JP-5, or JP-8 jet fuel vapor induce persisting changes in protein expression, CNS neurotransmitters levels, and neurobehavioral capacity in rats. While observational analysis of chronically exposed animals may indicate no apparent deficits, use of appropriate neurobehavioral tests may reveal significant changes in sensory, motivational, fine motor, and higher cognitive capacity.…”

Section: Hydrocarbon Fuel Neurotoxicity 293mentioning

confidence: 99%

A Review of the Neurotoxicity Risk of Selected Hydrocarbon Fuels

Ritchie¹

2001

Journal of Toxicology and Environmental Health, Part B

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Over 1.3 million civilian and military personnel are occupationally exposed to hydrocarbon fuels, emphasizing gasoline, jet fuel, diesel fuel, or kerosene. These exposures may occur acutely or chronically to raw fuel, vapor, aerosol, or fuel combustion exhaust by dermal, respiratory inhalation, or oral ingestion routes, and commonly occur concurrently with exposure to other chemicals and stressors. Hydrocarbon fuels are complex mixtures of 150-260+ aliphatic and aromatic hydrocarbon compounds containing varying concentrations of potential neurotoxicants including benzene, n-hexane, toluene, xylenes, naphthalene, and certain n-C9-C12 fractions (n-propylbenzene, trimethylbenzene isomers). Due to their natural petroleum base, the chemical composition of different hydrocarbon fuels is not defined, and the fuels are classified according to broad performance criteria such as flash and boiling points, complicating toxicological comparisons. While hydrocarbon fuel exposures occur typically at concentrations below permissible exposure limits for their constituent chemicals, it is unknown whether additive or synergistic interactions may result in unpredicted neurotoxicity. The inclusion of up to six performance additives in existing fuel formulations presents additional neurotoxicity challenge. Additionally, exposures to hydrocarbon fuels, typically with minimal respiratory or dermal protection, range from weekly fueling of personal automobiles to waist-deep immersion of personnel in raw fuel during maintenance of aircraft fuel tanks. Occupational exposures may occur on a near daily basis for from several months to over 20 yr. A number of published studies have reported acute or persisting neurotoxic effects from acute, subchronic, or chronic exposure of humans or animals to hydrocarbon fuels, or to certain constituent chemicals of these fuels. This review summarizes human and animal studies of hydrocarbon fuel-induced neurotoxicity and neurobehavioral consequences. It is hoped that this review will support ongoing attempts to review and possibly revise exposure standards for hydrocarbon fuels.

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Proteomic analysis of simulated occupational jet fuel exposure in the lung

Cited by 38 publications

References 46 publications

Depletion of Liver Glutathione Levels in Rats: A Potential Confound of Nose-Only Inhalation

Depletion of Liver Glutathione Levels in Rats: A Potential Confound of Nose-Only Inhalation

In vivo comparison of epithelial responses for S-8 versus JP-8 jet fuels below permissible exposure limit

A Review of the Neurotoxicity Risk of Selected Hydrocarbon Fuels

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