Considerations for Development of Exposure Limits for Chemicals Encountered During Aircraft Operation.

BACKGROUND: Military aircrews' health status is critical to their mission readiness, as they perform physically and cognitively demanding tasks in nontraditional work environments. Research Objectives: Our objective is to develop a broad operational risk assessment framework and demonstrate its applicability to health risks to aircrews because of airborne chemical exposure, considering stressors such as heat and exertion. METHODS: Extrapolation of generic exposure standards to military aviation-specific conditions can include computation of risk-relevant internal dosimetry estimates by incorporating changes in breathing patterns and blood flow distribution because of aspects of the in-flight environment. We provide an example of the effects of exertion on peak blood concentrations of 1,2,4-trimethylbenzene computed using a physiologically based pharmacokinetic model. RESULTS: Existing published collections on the effects of flight-related stressors on breathing patterns and blood flow address only a limited number of stressors. Although data exist that can be used to develop operational exposure limits specific to military aircrew activities, efforts to integrate this information in specific chemical assessments have been limited. CONCLUSIONS: Efforts to develop operational exposure limits would benefit from guidance on how to make use of existing assessments and expanded databases of the impact of environmental stressors on adult human physiology.

Riding (High) into the danger zone: a review of potential differences in chemical exposures in fighter pilots resulting from high altitude and G-forces.

INTRODUCTION: When in flight, pilots of high performance aircraft experience conditions unique to their profession. Training flights, performed as often as several times a week, can expose these pilots to altitudes in excess of 15 km (~50,000 ft, with a cabin pressurized to an altitude of ~20,000 ft), and the maneuvers performed in flight can exacerbate the G-forces felt by the pilot. While the pilots specifically train to withstand these extreme conditions, the physiologic stress could very likely lead to differences in the disposition of chemicals in the body, and consequently, dangerously high exposures. Unfortunately, very little is known about how the conditions experienced by fighter pilots affects chemical disposition. Areas covered: The purpose of this review is to present information about the effects of high altitude, G-forces, and other conditions experienced by fighter pilots on chemical disposition. Using this information, the expected changes in chemical exposure will be discussed, using isopropyl alcohol as an example. Expert opinion: There is a severe lack of information concerning the effects of the fighter pilot environment on the pharmacokinetics and pharmacodynamics of chemicals. Given the possibility of exposure prior to or during flight, it is important that these potential effects be investigated further.

Characterization of exposure to byproducts from firing lead-free frangible ammunition in an enclosed, ventilated firing range.

U.S. Air Force small arms firing ranges began using copper-based, lead-free frangible ammunition in the early 2000s due to environmental and health concerns related to the use of lead-based ammunition. Exposure assessments at these firing ranges have routinely detected chemicals and metals in amounts much lower than their mass-based occupational exposure limits, yet, instructors report work-related health concerns including respiratory distress, nausea, and headache. The objective of this study at one firing range was to characterize the aerosol emissions produced by weapons during firing events and evaluate the ventilation system's effectiveness in controlling instructor exposure to these emissions. The ventilation system was assessed by measuring the range static air pressure differential and the air velocity at the firing line. Air flow patterns were near the firing line. Instructor exposure was sampled using a filter-based air sampling method for metals and a wearable, real-time ultrafine particle counter. Area air sampling was simultaneously performed to characterize the particle size distribution, morphology, and composition. In the instructor's breathing zone, the airborne mass concentration of copper was low (range = <1 µg/m3 to 16 µg/m3), yet the ultrafine (nanoscale) particle number concentration increased substantially during each firing event. Ultrafine particles contained some copper and were complex in morphology and composition. The ventilation assessment found that the average velocity across all shooting lanes was acceptable compared to the recommended guideline (20% of the ideal 0.38 m/s (75 ft/min). However, uniform, downrange airflow pattern requirements were not met. These results suggest that the mass-based occupational exposure limits, as applied to this environment, may not be protective enough to eliminate health complaints reported by instructors whose full-time job involves training personnel on weapons that fire lead-free frangible ammunition. Using an ultrafine particle counter appears to be an alternative method of assessing ventilation effectiveness in removing ultrafine particulate produced during firing events.

Dimerization Products of Chloroprene are Background Contaminants Emitted from ALTEF (Polyvinylidene Difluoride) Gas Sampling Bags.

Gas sampling bags have been used for collecting air samples. Tedlar bags are most commonly used, but bleed background chemicals such as N,N-dimethylacetamide and phenol. It is often necessary to remove the contaminant by flushing the bags with pure nitrogen or air. In this study, we identified four chloroprene dimerization products as background contaminants emitted from ALTEF bags that are made of a proprietary polyvinylidene difluoride (PVDF). No monomer chloroprene was detected in the bags analyzed. All of the dimers gradually increased once bags were filled with nitrogen due to diffusion from the bag surface. Flushing the bags with nitrogen reduced their concentrations, but was not effective for removing the contaminants. When the bags that had been flushed with nitrogen 5 times were left for 24 h, they increased again, indicating that the dimers were constantly emitted from the ALTEF bag surface. To our knowledge, these compounds have never been demonstrated in ALTEF or other PVDF bags. Our finding indicates that ALTEF might be incorporated with Neoprene (chloroprene-based polymer) during its manufacturing process.

Storage stability of exhaled breath on Tenax TA.

Exhaled breath is coming to the forefront of non-invasive biomarker discovery efforts. Concentration of exhaled breath volatile organic compounds (VOCs) on thermal desorption (TD) tubes with subsequent analysis by gas chromatography-mass spectrometry (GC-MS) has dominated this field. As discovery experimentation increases in frequency, the need to evaluate the long-term storage stability of exhaled breath VOCs on thermal desorption adsorbent material is critical. To address this gap, exhaled breath was loaded on Tenax TA thermal desorption tubes and stored at various temperature conditions. 74 VOCs, 56 of which have been previously uncharacterized, were monitored using GC-MS over a period of 31 d. The results suggest that storage of exhaled breath at cold temperatures (4 °C) provides the most consistent retention of exhaled breath VOCs temporally. Samples were determined to be stable up to 14 d across storage conditions prior to gaining or losing 1-2 standard deviations in abundance. Through gene set enrichment analysis (GSEA), certain chemical classes were found to be positively (acids) or negatively (sulfur-containing) enriched temporally. By means of field sample collections, the effect of storage and shipping was found to be similar to those studies preformed in the laboratory at 4 °C. Collectively this study not only provides recommendations for proper storage conditions and storage length, but also illustrates the use of GSEA to exhaled breath based GC-MS data.

Depression Prevalence and Exposure to Organophosphate Esters in Aircraft Maintenance Workers.

INTRODUCTION: Previous studies found that aircraft maintenance workers may be exposed to organophosphates in hydraulic fluid and engine oil. Studies have also illustrated a link between long-term low-level organophosphate pesticide exposure and depression. METHODS: A questionnaire containing the Patient Health Questionnaire 8 depression screener was e-mailed to 52,080 aircraft maintenance workers (with N = 4801 complete responses) in a cross-sectional study to determine prevalence and severity of depression and descriptions of their occupational exposures. RESULTS: There was no significant difference between reported depression prevalence and severity in similar exposure groups in which aircraft maintenance workers were exposed or may have been exposed to organophosphate esters compared to similar exposure groups in which they were not exposed. However, a dichotomous measure of the prevalence of depression was significantly associated with self-reported exposure levels from low (OR: 1.21) to moderate (OR: 1.68) to high exposure (OR: 2.70) and with each exposure route including contact (OR: 1.68), inhalation (OR: 2.52), and ingestion (OR: 2.55). A self-reported four-level measure of depression severity was also associated with a self-reported four-level measure of exposure. DISCUSSION: Based on self-reported exposures and outcomes, an association is observed between organophosphate exposure and depression; however, we cannot assume that the associations we observed are causal because some workers may have been more likely to report exposure to organophosphate esters and also more likely to report depression. Future studies should consider using a larger sample size, better methods for characterizing crew chief exposures, and bioassays to measure dose rather than exposure. Hardos JE, Whitehead LW, Han I, Ott DK, Waller DK. Depression prevalence and exposure to organophosphate esters in aircraft maintenance workers. Aerosp Med Hum Perform. 2016; 87(8):712-717.

The identification of hypoxia biomarkers from exhaled breath under normobaric conditions.

Pilots have reported experiencing in-flight hypoxic-like symptoms since the inception of high-altitude aviation. As a result, the need to monitor pilots, in-flight, for the onset of hypoxic conditions is of great interest to the aviation community. We propose that exhaled breath is an appropriate non-invasive medium for monitoring pilot hypoxic risk through volatile organic compound (VOC) analysis. To identify changes in the exhaled breath VOCs produced during periods of reduced O2 levels, volunteers were exposed to simulated flight profiles, i.e. sea level for 5 min, O2 levels found at elevated altitudes for 5 min or placebo and 5 min at 100% O2 recovery gas, using a modified flight mask interfaced with a reduced O2 breathing device. During the course of these test events, time series breath samples from the flight mask and pre/post bag samples were collected and analyzed by gas chromatography/mass spectrometry (GC/MS). Seven compounds (pentanal, 4-butyrolactone, 2-pentanone, 2-hexanone, 2-cyclopenten-1-one, 3-methylheptane and 2-heptanone) were found to significantly change in response to hypoxic conditions. Additionally, the isoprene, 2-methyl-1,3-butadiene, was found to increase following the overall exposure profile. This study establishes an experimental means for monitoring changes in VOCs in response to hypoxic conditions, a computational workflow for compound analysis via the Metabolite Differentiation and Discovery Lab and MatLab(©) software and identifies potential volatile organic compound biomarkers of hypoxia exposure.

Detection of volatile organic compounds indicative of human presence in the air.

Volatile organic compounds were collected and analyzed from a variety of indoor and outdoor air samples to test whether human-derived compounds can be readily detected in the air and if they can be associated with human occupancy or presence. Compounds were captured with thermal desorption tubes and then analyzed by gas chromatography with mass spectrometry. Isoprene, a major volatile organic compound in exhaled breath, was shown to be the best indicator of human presence. Acetone, another major breath-borne compound, was higher in unoccupied or minimally occupied areas than in human-occupied areas, indicating that its majority may be derived from exogenous sources. The association of endogenous skin-derived compounds with human occupancy was not significant. In contrast, numerous compounds that are found in foods and consumer products were detected at elevated levels in the occupied areas. Our results revealed that isoprene and many exogenous volatile organic compounds consumed by humans are emitted at levels sufficient for detection in the air, which may be indicative of human presence.

Evaluation of Bio-VOC Sampler for Analysis of Volatile Organic Compounds in Exhaled Breath.

Monitoring volatile organic compounds (VOCs) from exhaled breath has been used to determine exposures of humans to chemicals. Prior to analysis of VOCs, breath samples are often collected with canisters or bags and concentrated. The Bio-VOC breath sampler, a commercial sampling device, has been recently introduced to the market with growing use. The main advantage for this sampler is to collect the last portion of exhaled breath, which is more likely to represent the air deep in the lungs. However, information about the Bio-VOC sampler is somewhat limited. Therefore, we have thoroughly evaluated the sampler here. We determined the volume of the breath air collected in the sampler was approximately 88 mL. When sampling was repeated multiple times, with the succeeding exhalations applied to a single sorbent tube, we observed linear relationships between the normalized peak intensity and the number of repeated collections with the sampler in many of the breath VOCs detected. No moisture effect was observed on the Tenax sorbent tubes used. However, due to the limitation in the collection volume, the use of the Bio-VOC sampler is recommended only for detection of VOCs present at high concentrations unless repeated collections of breath samples on the sampler are conducted.