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Abstract

Fresh and used aircraft engine lubricants (Mobil Jet Oil II) were analysed using a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICRMS) and comprehensive two dimensional gas chromatography with high resolution time of flight mass spectrometry (GCxGC-HRTOFMS). The composition of the fresh oil was established, with special focus to its tricresyl phosphate (TCP) content as this has formed the focus for most investigations into aerotoxic syndrome. The results showed that only four TCP isomers were present at detectable levels in the fresh oil: mmm-TCP, mmp-TCP, ppm-TCP and ppp-TCP. The results indicate that the formulation of Mobile Jet Oil II does not contain the more toxic ortho substituted TCP isomers at concentrations above 0.0005%. The temperatures of jet engines during operation are greater than 200 °C which creates the potential to alter the composition of the original oil and create other toxic compounds. The results show there may be a significant risk from alkylated cresyl phosphates, which were identified in the used oils at concentrations calculated in the range of 0.13–0.69%. w/w. Several xylenyl and ethylphenyl phosphates have been shown to exhibit a similar toxicity to ortho substituted TCP isomers which makes there discovery in used oil significant. These compounds should be included in future aircraft air quality studies and when assessing the risks and causes of aerotoxic syndrome.

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... The dirty socks or smelly feet description, often used, is increasingly understood to be related to the thermal degradation and hydrolysis of the oil base stocks. In most aircraft engine oils, a hazardous substance that can be found is tricresyl phosphate, a compound with proven toxicity [24][25][26][27]. Moreover, the high temperatures attained in aircraft jet engines may cause thermal pyrolysis able to produce potentially toxic, still not well defined, chemical substances [25,28]. ...
... In most aircraft engine oils, a hazardous substance that can be found is tricresyl phosphate, a compound with proven toxicity [24][25][26][27]. Moreover, the high temperatures attained in aircraft jet engines may cause thermal pyrolysis able to produce potentially toxic, still not well defined, chemical substances [25,28]. Besides, respiratory, and neurological toxicity derived from exposure to nanoparticles released by bleed air systems in the breathing air of commercial aircraft has also been reported [29]. ...
... Other contamination sources may include hydraulic fluids or flame retardants emanating from the highly flame-protected environment of airplanes [30]. Minimization of potential contaminating sources and/or improved reduction of pollutants by air cleaning should be mandatory to diminish the risk of AS [1][2][3][4][5][6][7][8][9][24][25][26]. An important device for air cleaning in aircraft are HEPA filters, and improving their efficacy would decrease the risk of infection caused by airborne microorganisms such as SARS -CoV 2, A/H1N1 influenza virus, and others [1,[31][32][33] Nowadays, many clinicians are not aware of the existence of AS; hence, when patients require medical assistance after a fume event, the lack of a good, standardized protocol precludes general recommendations on the immediate identification of the implicated chemical toxins, on the type of pulmonary and neurological studies to perform, and on the therapeutic management of the disease [1]. ...
Article
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PurposeCase series on respiratory features of Aerotoxic Syndrome (AS). The term AS has been coined to describe the spectrum of clinical manifestations after aircraft fume events. Among these manifestations, neurological and respiratory symptoms are the most frequently reported complaints.Methods Three cases of AS with relevant respiratory features are presented.ResultsCough and shortness of breath for 6 to12 months were the predominant symptoms in the first two cases. The first case also developed neurological symptoms affecting his central nervous system. In the third case, the patient complained for nine years about an unbearable cough triggered by odors, smells, and a variety of indoor and outdoor irritants, among other symptoms of multiple chemical sensitivity. In all three cases, the respiratory symptoms resolved after appropriate treatment.Conclusion Our report aims at raising awareness on AS and calls for actions to improve the management of patients suffering from this syndrome.
... To assess the risks from aircraft oil Megson et al. (2016) analysed samples of fresh and used oil. The 51 results showed that only four non-ortho substituted TCP isomers were identified at detectable levels in 52 the fresh and used oil (mmm-TCP, mmp-TCP, ppm-TCP and ppp-TCP). ...
... Despite the removal of ToCP from oil several studies have detected ToCP in aircraft 55 cabins (Crump et al., 2011, Rosenberger et al., 2013, Ramsden, 2013). The studies undertaken on aircraft 56 oil show a slight variability between the proportions of TCP isomer present in different samples, brands 57 and depending on if the oil is used or fresh ( Hecker et al., 2014, Megson et al., 2016. 58 ...
... Much debate on the potential cause of aerotoxic syndrome has focused on ToCP. This was believed to 119 originate from aircraft oil, however Megson et al. (2016) analysed samples of fresh and used oil and 120 identified that only four non-ortho substituted TCP isomers were present. Despite the removal of ToCP 121 from oil several studies have continued to detect ToCP in aircraft cabins (Crump et al., 2011, 122 Rosenberger et al., 2013, Ramsden, 2013. ...
... Acute onset and chronic symptoms that have been associated with occupational exposure include irritation of the eyes, nose, and throat, disorientation, headaches, dizziness, numbness, cardiovascular concerns, tremors, and cognitive problems (Winder and Balouet, 2000). In response to the concern about the neurotoxicity of Triortho-Cresyl Phosphate (ToCP), concentrations have been reduced in oil formulations resulting in the absence of detectable levels of ortho isomers of TCP in new or used aircraft oil (Winder and Balouet, 2002;Megson et al., 2016Megson et al., , 2019. ToCP, other TCP isomers, other organophosphates (OPs), and VOC concentrations on monitored flights have been reported at concentrations well below traditional safety guidelines, often falling below limits of detection; this has led to the belief by some that "Aerotoxic Syndrome" may not be an occupational illness (Wolkoff et al., 2015;de Ree et al., 2014). ...
... However, these substances make up only a portion of what one is potentially exposed to onboard the aircraft (Winder and Balouet, 2002). High-Resolution Mass Spectrometry allows for non-targeted analysis (Kauffman, 2014;Cavanna et al., 2018;Megson et al., 2016). This technique allows for the tentative identification of detectable compounds within the exposome without prior knowledge of the compound's existence (Cavanna et al., 2018). ...
Article
Occupational exposure to oil fumes, organophosphates, halogenated flame retardants, and other volatile and semi-volatile contaminants is a concern within the aviation industry. There is no current consensus on the risk attributed to exposure to these chemical classes within the aircraft cabin. Contaminant concentrations rarely exceed conventional air quality guidelines, but concerns have been raised about these guidelines' applicability within the aircraft environment. This systematic review, the largest and most comprehensive completed to date on the subject matter, aims to synthesize the existing research related to chemical and other exposures inside the aircraft cabin to determine the occupational risk that may be attributed said exposure, as well as, determine knowledge gaps in source, pathway, and receptor that may exist. The Science Direct, Scopus, and Web of Science databases were queried with five search terms generating 138 manuscripts that met acceptance criteria and screening.. Several potential areas requiring future examination were identified: Potable water on aircraft should be examined as a potential source of pollutant exposure, as should air conditioning expansion turbines. Historical exposure should also be more fully explored, and non-targeted analysis could provide valuable information to comprehend the aircraft cabin exposome. Occupational risk under typical flight scenarios appears to be limited for most healthy individuals. Contaminants of concern were demonstrated to be extant within the cabin, however the concentrations under normal circumstances do not appear to be individually responsible for the symptomologies that are present in impacted individuals. Questions remain regarding those that are more vulnerable or susceptible to exposure. Additionally, establishing the effects of chronic low dose exposure and exposure to contaminant mixtures has not been satisfied. The risk of acute exposure in mitigable fume events is substantial, and technological solutions or the replacement of compounds of concern for safer alternatives should be a priority.
... Data can also be re-evaluated later to check for the presence of other potential contaminants of concern without the need for re-analysis. This allowed Megson et al. [119] to identify an additional group of toxic organophosphates in jet oil following an initial screening exercise in a forensic investigation. Finally if a new potential POP is discovered its presence can be checked for in historic samples to identify when it arrived in the environment. ...
... There have been many instances where chemical impurities or co-contaminants present in samples have revealed some key information in an environmental forensics investigation. Recent examples include 2,4,6,8-Tetrachlorodibenzothiophene as an impurity in 2,4-D production from a specific manufacturer in Newark Bay [161] impurities in dechlorane plus production from a manufacturer in the Niagara region [162], and xylenyl cresyl phosphates in used jet oil [119]. Had just the main contaminant in question been determined in these investigations then this key diagnostic information would not have been recorded. ...
Article
The field of environmental forensics emerged in the 1980s as a consequence of legislative frameworks enacted to enable parties, either states or individuals, to seek compensation with regard to contamination or injury due to damage to the environment. This legal environment requires stringent record keeping and defendable data therefore analysis can sometimes be confined to data to be obtained from certified laboratories using a standard accredited analytical method. Many of these methods were developed to target specific compounds for risk assessment purposes and not for environmental forensics applications such as source identification or age dating which often require larger data sets. The determination of persistent organic pollutants (POPs) for environmental forensic applications requires methods that are selective but also cover a wide range of target analytes which can be identified and quantified without bias. POPs are used in a wide variety of applications such as flame retardants, fire suppressants, heat transfer agents, surfactants and pesticides mainly because of their chemical inertness and stability. They also include compounds such as dioxins that can be unintentionally produced from industrial activities. POPs are persistent in the environment, bioaccumulative and/or toxic and therefore require analytical methods that are sensitive enough to meet the low detection limits needed for the protection of the environment and human health. A variety of techniques, procedures and instruments can be used which are well suited for different scenarios. Optimised methods are important to ensure that analytes are quantitatively extracted, matrix coextractables and interferences are removed and instruments are used most effectively and efficiently. This can require deviation from standard methods which can open the data up to further scrutiny in the courtroom. However, when argued effectively and strict QA/QC procedures are followed the development and optimisation of methods based on investigation specific scenarios has the potential to generate better quality and more useful data.
... In this testing system, not just temperature but also the confined oil and the curved metal surface impact the outcome of the examination. Although the oil is a proprietary multi-component mixture, the literature [29] and the FT-IR spectrum of the fresh lubricant ( Figure S1) suggest that its main constituents are m-phthalates, aliphatic esters, and phosphates with long alkyl chains. The spectrum serves to assist with the understanding of the thermal degradation and subsequent carbonization behaviors of the oil rather than to determine the precise components. ...
Article
Full-text available
We created a coke-repellent inner surface in a stainless steel (SS-321) tube using an enhanced chemical etching tactic. A water-borne etching solution was formulated by combining an ion sequestering ligand (L), hydrogen peroxide (H), hydrochloric acid (C), and a stabilizing agent (E or N). Three etchants, LHC, LHC-E, and LHC-N, were therefore formulated, respectively. The coke-repellent metal surfaces achieved by these etchants all show a characteristic topographic pattern on a micron scale, specifically with grooved spherulite and ridge-like topographic patterns. Fundamentally, these two topographic patterns prompt overhead micro turbulence fields whose agitation mitigates the surface entrapment of aromatic hydrocarbon flocs generated from the overhead lubricant. The surface entrapment of flocs is the crucial step to trigger coke growth. The coke repellency was assessed by placing an SS-321 tube filled with a lubricant in a heat soak. It was found that the topographic pattern and its surface roughness level have opposite effects on coke development. Hence, the three etchants give rise to different coke-resilient surfaces. Moreover, the plug flow rate of the etchant also affects the anti-coking performance, exhibiting an optimal flow rate that offers the highest coke-proof efficacy.
... 28 Lately, efforts have been made to evaluate the applicability of GC×GC with high-resolution quadrupole time-of-flight mass spectrometry (accQTOFMS), which provides high mass-resolving power and capability for accurate mass measurements (<5 ppm). [50][51][52][53] Such features narrow the compound identification range, which greatly simplifies metabolite annotation and identification. Although the acquisition rate is slower com- ...
Article
Full-text available
The detection of human-derived metabolites as potential diagnostic biomarkers of genetic disorders, metabolic diseases, systemic diseases, and infectious diseases has been much studied in recent years, especially as technical capabilities improve, and statistical procedures are increasingly able to tease critical chemical attributes from complex data sets. Given the complex distribution of human biological matrices, the characterization and/or identification of these chemical entities is technically challenging, and is often confounded by incomplete chromatographic resolution or insufficient discriminatory power of the mass spectrometry (MS) domain. Recently, comprehensive two-dimensional gas chromatography (GC×GC) has evolved into a mature higher separation order technique that offers unprecedented resolving power, which in turn can greatly advantage clinical metabolomics studies via the expansion of metabolite coverage. In this contribution, the current state of knowledge in the development of GC×GC coupled to MS as a high-resolution bioanalytical technique for the analysis of clinical metabolites is reviewed. Selected recent applications (years 2012 to 2021) that emphasize improved GC×GC-MS strategies for clinical human metabolites' detection, identification, and quantitative analysis are described. In addition, we share our perspectives on current challenges and potential future directions of GC×GC in clinical applications.
... Eine kurz zurückliegende Analyse von frischem und gebrauchtem "Mobil Jet Oil II" mittels zweidimensionaler Gaschromatographie mit hochauflösender Time of Flight Massenspektroskopie (GCxGC-HRTOFMS) ergab keinen Nachweis von ortho-Kresyl-Isomeren (< 0,0005 %) mehr. Es wurden lediglich die Isomeren m,m,m-TKP, m,m,p-TKP, p,p,m-TKP und p,p,p-TKP in einem Konzentrationsbereich zwischen 0,5 und 1,7 % nachgewiesen (Megson et al. 2016). In neueren Untersuchungen zur Luftqualität in Verkehrsflugzeugen konnten ebenfalls keine ortho-Isomeren des TKP gefunden werden, während meta-und para-Isomeren lediglich in Spuren zu finden waren (< 1 µg/m 3 ) (Solbu et al. 2011, Houtzager et al. 2014, Rosenberger 2018, Schuchardt et al. 2019. ...
Article
Umweltmed – Hygiene – Arbeitsmed 25 (1) 7 – 15 (2020): „Fume and Smell Events“ are incidents in aircrafts which come along with odor development or visible fumes in aircraft cabin or cockpit. After those events air crews report a heterogeneous and complex set of health effects including severe short- and long-term ill-health effects. Particularly two classes of chemicals with neurotoxic modes of action are currently discussed to be possibly responsible for reported health effects. 1. Organophosphorous compounds incl. tricresyl phosphates originating from additives in turbine and hydraulic oils or from flame retardants can contaminate cabin air either by the bleed air system or by fumigation from flame-protected components. 2. Volatile organic compounds (VOC) incl. neurotoxic n-hexane or toluene from in most cases so far unknown origin. According to the state of knowledge in biomonitoring aircrews are exposed to some higher extent to particular organophosphorous compounds than the general population but less exposed than aircraft technicians with contact to hydraulic and turbine oils. Neurotoxic ortho isomers of tricresyl phosphates have not been found in body fluids of technicians, air crews or the general population. The only sparse biomonitoring data on exposure of air crews to VOC hint to an existing, but rather small burden, particularly with neurotoxic VOC. Comparing biomonitoring data with current threshold limit values reveal that neither organophosphorous compounds nor neurotoxic VOC can be responsible for reported health effects.
... An ideal ionization process should maintain both the MS fingerprinting capability and the MI information; to pursue such an objective different "soft" ionization technologies have been exploited in the GC × GC-MS field, such as photon ionization [9,10], chemical ionization [11], supersonic molecular beam (SMB) EI [12][13][14], atmospheric pressure chemical ionization [15], variable EI [16,17], and field ionization [18]. In particular, the use of photon ionization and SMB EI have been strongly-emphasized forms of soft ionization for GC × GC-MS analyses [9,10,[12][13][14]. ...
Article
The present research is based on the use of comprehensive two-dimensional gas chromatography-quadrupole mass spectrometry (GC × GC-QMS), using “milder” electron ionization (EI) conditions. The term milder refers to the use of lower energy EI conditions (e.g., 20 eV), instead of the most common electron energy of 70 eV. The effects of using lower source temperatures were also evaluated. Within such an analytical context, GC × GC-QMS was applied to the analysis of a variety of different molecular-mass compounds with various polarities (sterols, linear alkanes, fatty acid methyl esters, vitamin E, squalene, a linear alcohol, and a group of fifteen pesticides). In general, the results attained indicate that milder EI conditions, and lower source temperatures, generate mass spectra with a higher relative abundance of ions at higher mass-over-charge (m/z) values, comprising the molecular ion, and reduced fragmentation at lower m/z values. The extent to which such a phenomenon occurred was obviously related to the chemical structure of each analyte. Spectral repeatability was also assessed, and was found to be satisfactory. Finally, with regard to analyte signal-to-noise ratios these were generally comparable in applications involving different electron ionization energies.
... TMPP is considered to be hazardous for the environment and toxic to aquatic organisms and is harmful if swallowed or allowed to have contact with skin. TMPP can cause organophosphate-induced delayed neuropathy which can lead to nerve degeneration (WHO, 1990;Ehrich and Jortner, 2002) and may be the cause of aerotoxic syndrome (Megson et al., 2016). However, the toxicity of TMPP is largely based on the o-TMPP (o,o,o) isomer content (De Nola et al., 2008), which led to its elimination from commercial products (van der Veen and de Boer, 2012). ...
Article
Organophosphate esters (OPEs) are commonly used as flame retardants (FRs) and plasticizers. The usage of OPEs has increased recently due to the ban of several brominated flame retardants, but information on levels in the environment, including the indoor environment is still limited. We investigated the occurrence and distribution of 12 OPEs in urban house dust from Vancouver, Canada; Istanbul, Turkey; and Cairo, Egypt. The median ∑OPE concentration was 41.4 μg/g in the Vancouver samples while median levels in Istanbul and Cairo were significantly lower. The median composition profiles of OPEs in Vancouver and Cairo were dominated by tris (2-butoxyethyl) phosphate (TBOEP), accounting for 56 and 92% of total OPEs respectively while it showed a detection frequency of only 14% in Istanbul. Tris (2-chloropropyl) phosphate (TCPP) was the most abundant chlorinated OPE representing 20 and 36% of the total OPEs in Vancouver and Istanbul respectively, but was below the detection limit in the Cairo dust samples. Consistent with other studies, ΣOPE concentrations were ~1 to 2 orders of magnitude higher than PBDEs and currently used flame retardants in the same dust samples. The mean estimated daily intakes (EDI) of ΣOPE from dust were 115, 38 and 9 ng/kg/bw/day in Vancouver, Cairo and Istanbul respectively for toddlers where adults were ~10 times lower. The total toddler OPE intake ranged from 115 to 2900, 38 to 845 and from 9 to 240 ng/kg bw/day across the three cities. TBOEP had the largest contribution to the EDI in both toddler and adults, where toddler TBOEP exposures via dust represented 4% to 80%, 2% to 44% and 0.1% to 6% of the Reference Doses (RfD) in the mean and high intake scenarios for toddlers in Vancouver, Cairo and Istanbul respectively.
... My observed increased sensitivity to air pollution weeks and months after the actual intoxication event is in line with reports of increased bronchial reactivity after exposure to polluted air, i.e. the dust of the World Trade Center explosion at the terrorist attacks of 9/11 in 2001 [43] [44] [45] [46] [47]; in particular, a persistent hyperreactivity and reactive airway dysfunction was observed in the people exposed to this toxic dust [48]. The case where the air inside the airplane after landing caused dyspnea and chest pain symptoms is in line with the inhalation of polluted air with toxic fumes in the airline cabin (aerotoxic syndrome) [49] [50] [51]. The appearance of hemangioma in the months after the exposure may not be coincidental since an increased incidence of hemangioma was reported to be associated with exposure to toxic substance, e.g. ...
... The MS/MS filters that were described in the above section are also applicable for full-scan MS data reduction. For example, features such as mass defects, isotope patterns, accurate mass and ion intensities were used to filter full scan data for characterizing tricresyl phosphate isomers in aircraft engine lubricants that are linked to aerotoxic syndrome in aircraft crew (Megson et al., 2016) and halogenated persistent organics in an electronics recycling facility's dust (Ubukata et al., 2015). Typically, each molecular feature extracted from the raw HRMS data file has its own accurate mass and measured m/z values, and a characteristic retention time but with small differences between samples. ...
Article
Organophosphate esters are an emerging environmental concern since they spread persistently across all environmental compartments (air, soil, water, etc.). Measurements of semivolatile organic compounds are important but not without challenges due to their physicochemical properties. Selected ion flow tube-mass spectrometry (SIFT-MS) can be relevant for their analysis in air because it is a direct analytical method without separation that requires little preparation and no external calibration. SIFT-MS is based on the chemical reactivity of analytes with reactant ions. For volatile and semivolatile organic compound analysis in the gas phase, knowledge of ion-molecule reactions and kinetic parameters is essential for the utilization of this technology. In the present work, we focused on organophosphate esters, semivolatile compounds that are now ubiquitous in the environment. The ion-molecule reactions of eight precursor ions that are available in SIFT-MS (H3O+, NO+, O2•+, OH-, O•-, O2•-, NO2-, and NO3-) with six organophosphate esters were investigated. The modeling of ion-molecule reaction pathways by calculations supported and complemented the experimental work. Organophosphate esters reacted with six of the eight precursor ions with characteristic reaction mechanisms, such as protonation with hydronium precursor ions and association with NO+ ions, while nucleophilic substitution occurred with OH-, O•-, and O2•-. No reaction was observed with NO2- and NO3- ions. This work shows that the direct analysis of semivolatile organic compounds is feasible using SIFT-MS with both positive and negative ionization modes.
Chapter
The combined use of multidimensional gas chromatography (MDGC)—in either heart-cutting or comprehensive configuration—to mass spectrometry (MS) generates a very powerful three-dimensional platform. The potential of MDGC-MS within the context of various scenarios is herein described and highlighted; technical aspects related to such a hyphenation are also discussed. The combination of heart-cutting MDGC with MS is much more established and is characterized by no specific technical difficulties (practically the same as for GC-MS instrumentation). For such a reason, particular focus will be devoted to the combination comprehensive MDGC-MS, and on aspects related to its evolution mainly after 2010.
Article
Endothermic displacement reactions between proton bound dimers of organophosphorus compounds (OPCs) and isopropanol (IPA) were enabled in air at ambient pressure with tandem differential mobility spectrometry (DMS). Proton bound dimers (M2H+) were mobility isolated in purified air with a first DMS stage, mixed with IPA at ≥100 ppm in a middle reactive stage at 106 to 160 Td from a symmetrical 4 MHz waveform, and mobility analyzed in a second DMS stage. Although the enthalpy for displacement of M by IPA in M2H+ is unfavorable by +44 to 50 kJ mol-1, formation of the heterogenous proton bound dimer, MH+(IPA) arises from field induced dissociation of M2H+ to MH+ and addition of IPA. While peak dispersion for M2H+ of OPCs is limited to -2.25 to -0.5 V compensation voltage, peaks for MH+(IPA) were located at -10.5 to -8.25 V through a combination of ion transformation and mobility-based vapor modification. This inaugural use of ion reactions in air at ambient pressure demonstrates that multi-stage sequential processing of ions can improve significantly the analytical performance in a mobility spectrometer.
Article
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There is little data available for the toxicity of used aircraft engine oils relative to their unused (new) versions. This study was conducted to determine if grade 3 (G3) and 4 (G4) aircraft engine oils in their new states (G3-N and G4-N) and their used versions (G3-U and G4-U) have the potential to induce toxicity via dermal application. Male and female Sprague Dawley rats were dermally exposed to water (control), new and used versions of G3 and G4 oils to determine the oil sub-chronic toxicity potentials. A volume of 300 μL of undiluted oil was applied to the pad of the Hill Top Chamber System©. Then the chamber was attached to a fur-free test site located at the back of the rat for 6 h/day for 5 consecutive days/week for 21 days (15 total exposures). Recovery rats also received similar treatments and were kept for 14 days post-exposure to screen for reversibility, persistence, or delayed occurrence of toxic effects. Both G3 and G4 oils had a significant impact on the weight of male and female reproductive organs: testes weights for recovery rats exposed to G3-N significantly decreased (12%) relative to controls; G3-N and G3-U decreased uterus weights by 23% and 29%, respectively; G4-N decreased uterus weights by 32% but were resolved at the end of the recovery period; G4-N increased the weight of the adrenals and spleen for females by 34% and 27%, respectively, during the recovery period. G3 and G4 induced more changes in female blood indices than in those for males. Of all versions of oils, G4-N induced the most changes in profiles of female blood. G4-N significantly decreased the white blood cells, lymphocytes, neutrophils, eosinophils and increased the mean platelet volumes. Interestingly, males were not affected by exposure to G4-N oil. While G3-N decreased the white blood cells and lymphocytes for females it slightly increased those for males. In summary, G3 and G4 oils impacted the weights for male and reproductive organs. This study highlights the health risks that aircraft maintenance workers may be exposed to if precautions are not taken to minimize exposure to these oils.
Chapter
Die systematische Untersuchung der Innenraumluft von Verkehrsflugzeugen auf chemische Stoffe und andere Luftqualitätsparameter wurde seit Beginn der 1990er Jahre international und seit 2009 in Deutschland intensiviert (Crump et al. 2011a und 2011b, Dechow et al. 1997, DeNola et al. 2008 und 2011, Guan et al. 2014a und 2014b, de Ree et al. 2014, Rosenberger 2012, Rosenberger et al. 2013, 2014 und 2016, Schuchardt et al. 2017, Solbu et al. 2011, Spengler et al. 2012, van Netten 2009). Die Gründe hierfür sind vielschichtig, wesentlich ist jedoch die Besorgnis insbesondere des fliegenden Personals über gesundheitsgefährdende Kabinenluft. Es wird angenommen, dass Emissionen von Schmierstoffbestandteilen aus dem Bereich der Antriebswellen in den Turbinen über das Belüftungssystem der Flugzeuge in die Kabine ursächlich für verschiedene Erkrankungen seien. Dabei stehen Additive der Turbinen- Öle, vornehmlich Trikresylphosphate (TKP, engl. TCP) sowie Hydraulikflüssigkeiten, die in der Regel ebenfalls phosphororganische Verbindungen (OPC engl. für organo phosphourus compounds) enthalten, im Vordergrund. Diskutiert werden aber auch Emissionen weiterer Stoffgruppen (flüchtige organische Verbindungen (VOC), Aldehyde oder organische Säuren) in die Kabine. Sehr häufig werden vermutete Einträge von Chemikalien mit Gerüchen assoziiert, woraufhin der Terminus „Smell Event“ geprägt wurde. Die Beobachtung von Rauch- oder Nebelbildung in der Kabine führte zum Begriff „Fume Event“. Für beide Begriffe liegen keine wissenschaftlichen begründeten Definitionen vor, so dass derzeit im Wesentlichen subjektive Eindrücke zu Geruchsepisoden meist unbekannter Genese als Handlungsgrundlage, z.B. für Abbrüche von Flügen, herangezogen werden. Für die Zusammenfassung der vielfältigen meist unspezifischen Gesundheitsbeeinträchtigungen wurde 2002 der Begriff des sogenannten „Aerotoxischen Syndroms“ eingeführt und bis heute diskutiert (vgl. auch Abschn. 3) (Winder u. Balouet 2002, Chaturvedi 2011, Harrison et al. 2016, de Boer et al. 2015, Schwarzer et al. 2014, Michaelis 2011). Das „Aerotoxische Syndrom“ ist medizinisch-wissenschaftlich nicht akzeptiert und stellt dementsprechend kein Krankheitsbild (Entität) dar. In diesem Beitrag werden die besonderen Bedingungen in Flugzeugkabinen beschrieben, mögliche chemische Stoffeinträge und deren Quellen aufgeführt, die hiermit verknüpften medizinischen Beschwerdebilder diskutiert, Methoden und Ergebnisse von Messungen in Flugzeugen zusammengefasst, um abschließend ein aktuelles bewertendes Gesamtbild zu beschreiben. Der vorliegende Beitrag fokussiert auf Verkehrsflugzeuge im herkömmlichen Sinne, wobei Untersuchungen von strahlgetriebenen Flugzeugen die wesentliche Basis zur Datenlage chemischer Innenraumluftverunreinigungen darstellen.
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Coal tar-based sealcoat (CTSC) products are an urban source of polycyclic aromatic compounds (PACs) to the environment. However, efforts to assess the environmental fate and impacts of CTSC-derived PACs are hindered by the ubiquity of (routinely monitored) PACs released from other environmental sources. To advance source identification of CTSC-derived PACs, we use comprehensive two-dimensional gas chromatography-high resolution mass spectrometry (GC×GC/HRMS) to characterize the major and minor components of CTSC products in comparison to those in other sources of PACs, viz., asphalt-based sealcoat products, diesel particulate, diesel fuel, used motor oil and roofing shingles. GC×GC/HRMS analyses of CTSC products led to the confident assignment of compounds with 88 unique elemental compositions, which includes a set of 240 individual PACs. Visualization of the resulting profiles using Kendrick mass defect plots and hierarchical cluster analysis highlighted compositional differences between the sources. Profiles of alkylated PAHs, and heteroatomic (N,O,S) PACs enabled greater specificity in source differentiation. Isomers of specific polycyclic aromatic nitrogen heterocycles (PANHs) were diagnostic for coal tar-derived PAC sources. The compounds identified and methods used for this identification are anticipated to aid in future efforts on risk assessment and source apportionment of PACs in environmental matrices.
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Toxicology is a new science, the complexities of which have been highlighted in the papers contained within this special section. Our understanding of the mechanisms through which various chemicals interfere with nervous system function is constantly evolving and research is unable to keep up with the speed with which new chemicals are produced and put onto the market. Thus there are often controversies surrounding the health-effects of commercially available compounds and disagreement around what constitutes safe exposure limits. This article will introduce readers to an emerging concern in this field, the potential risk to health of toxic fumes in airplane cabins. We explore the challenges and methodological issues encountered by researchers who have tried to investigate this issue and highlight the need for further research on this topic. We hope this article will promote discussion amongst academics and clinicians, and lead to the identification of creative solutions to the methodological issues encountered to date.
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Sensory effects in eyes and airways are common symptoms reported by aircraft crew and office workers. Neurological symptoms, such as headache, have also been reported. To assess the commonality and differences in exposures and health symptoms, a literature search of aircraft cabin and office air concentrations of non-reactive volatile organic compounds (VOCs) and ozone-initiated terpene reaction products were compiled and assessed. Data for tricresyl phosphates, in particular tri-ortho-cresyl phosphate (ToCP), were also compiled, as well as information on other risk factors such as low relative humidity.
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Contamination of the bleed air used to pressurize and ventilate aircraft cabins is of concern due to the potential health and safety hazards for passengers and crew. Databases from the Federal Aviation Administration, NASA, and other sources were examined in detail to determine the frequency of bleed air contamination incidents. The frequency was examined on an aircraft model basis with the intent of identifying aircraft make and models with elevated frequencies of contamination events. The reported results herein may help investigators to focus future studies of bleed air contamination incidents on smaller number of aircrafts. Incident frequency was normalized by the number of aircraft, number of flights, and flight hours for each model to account for the large variations in the number of aircraft of different models. The focus of the study was on aircraft models that are currently in service and are used by major airlines in the United States. Incidents examined in this study include those related to smoke, oil odors, fumes, and any symptom that might be related to exposure to such contamination, reported by crew members, between 2007 and 2012, for US based carriers for domestic flights and all international flights that either originated or terminated in the US. In addition to the reported frequency of incidents for different aircraft models, the analysis attempted to identify propulsion engines and auxiliary power units associated with aircrafts that had higher frequencies of incidents. While substantial variations were found in frequency of incidents, it was found that the contamination events were widely distributed across nearly all common models of aircraft. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Technical Report
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This study was set up in light of concerns about possible adverse impacts on the health and well-being of air crew resulting from exposure to substances in cabin air. The principal objectives were to analyse cabin air for volatile organic compounds (VOCs), semi-volatile organic compounds (SVOCs), particles and carbon monoxide (CO) in normal operations during all phases of flight (e.g. climb, cruise, descent), and to detect and characterise any anomalous elevations of VOC, SVOC and particle concentrations during any „fume events‟ or „air quality events‟ where unusual smells or similar occurrences were reported. A total of 100 flights in 5 different aircraft types were monitored in this way. Monitoring of the total VOC (TVOC) concentration was carried out using a photo-ionisation detector (PID). Samples were also collected onto sorbent tubes using a portable pump for subsequent laboratory analysis by thermal desorption/gas chromatography/mass spectrometry (TD/GC/MS) to determine specific VOCs and SVOCs. The PID was additionally used as a real-time detector of possible fume events. Carbon monoxide concentration and ultrafine particle count were determined using a gas monitor (electrochemical sensor) and P-Trak ultrafine particle counter, respectively. The sampling strategy allowed for a series of samples to be taken at defined points on all flights, with additional provision for samples of any „fume events‟ to be obtained immediately should they occur. These additional „air quality event‟ samples were initiated by the researcher conducting the measurements whenever any change in air quality was detected by the PID or ultrafine instruments, or reported by anyone on the aircraft. The protocol was designed to yield samples of these events that were directly comparable to the routine samples taken. The first part of the study involved monitoring on Boeing 757 cargo aircraft and included all necessary preparatory work for these operations, including equipment purchase, questionnaire design and protocol development. Subsequently Parts 2 to 5 of the study utilised the equipment and methods of Part 1 to carry out monitoring on Boeing 757, Airbus A320/1, BAe 146 and Airbus A319 passenger aircraft respectively. Flight crew and cabin crew (if any) were requested to complete a post-flight questionnaire for all flights. This included questions concerning any fumes or smells that occurred during the flight. It was also completed by the scientist conducting the air quality measurements. The flight staff were informed that the questionnaire was to be used in addition to normal fume event reporting procedures and that it did not replace them. No fume event occurred during this study which triggered the airline‟s formal reporting procedures. Sorbent tube samples were analysed for the following target compounds: Tri-ortho cresyl phosphate (TOCP); one of a number of TCP isomers, Other tri-cresyl phosphate (TCP) isomers; applications include a minor component of engine oil, Tri-butyl phosphate (TBP); applications include a component of hydraulic fluid, Toluene, m+p- xylenes, Limonene, Tetrachloroethylene (TCE), Undecane. Mean values (and percentiles) for VOC/SVOC concentrations are presented for all data (all samples for all flights and all flight phases), for each flight, for each flight phase, and for each part of the study (aircraft type). For ultrafine particles, TVOCs and CO, the number of flights (flight sectors) with levels within specified ranges are presented. More detailed data are provided in Part 2 of this report. Mean ultrafine particle numbers (all flight sectors) were always in the range 1,000-100,000 particles cm-3. On five flight sectors peak concentrations exceeded the maximum range of the instrument (500,000 particles cm-3). Mean total VOC concentrations were mostly below 2 ppm and a number of the short duration peak concentrations above 10 ppm were probably due to exposure to isopropyl alcohol vapour generated by the p-Trak instrument. Maximum CO concentrations were mostly below 2 ppm. The most abundant VOC/SVOCs were generally limonene and toluene. Highest concentrations of TBP, limonene, m+p-xylene and undecane occurred during first engine start, while TCE concentrations were highest during the „immediate‟ sampling period. Highest levels of TOCP, other TCPs and toluene occurred during climb, pre-landing and take-off respectively. A total of 30 air quality event sorbent tube samples were collected during the study. Numbers of events were similar in Parts 1, 2, 3 and 5 of the study, and highest in Part 4. Events were largely concentrated at engine start and take-off, with few occurring at top of climb or during cruise. Concentrations of target analytes during these events were not elevated compared with the routine samples collected in each respective phase of flight. A total of 38 flights had fumes or smells reported by at least one crew member or researcher in a post flight questionnaire. The dominant smell descriptor was „oil‟ or „oily‟, reported by 26 persons. Other descriptors were „sweet‟, „toilet smell‟, „exhaust‟, „chlorine‟, „de-icing fluid‟, „fuel‟, „heated dust‟ and „human waste‟. Four persons reported that the fumes/smells caused a health effect (headache or slight headache in all cases). Some flights had up to 3 persons reporting a smell/fume and others had only one person; a total of 60 (of 552) questionnaires reported a smell/fume. Some flights had reports of smells in more than one phase, and in two instances the smell of human waste was reported throughout the flight. On other flights, fumes/smells were reported during only one phase. The European standard ‘Aircraft internal air quality standards, criteria and determination methods‟(BS EN 4618: 2009) sets safety limits, health limits and comfort limits for a number of substances, including two that were measured in this study – carbon monoxide and toluene.The monitoring results indicate that concentrations of carbon monoxide did not exceed safety or health limits. Concentrations of carbon monoxide recorded during nine flights were equivalent to the 8h TWA (time weighted average) health limit, but this is believed to have been due to instrument malfunction rather than actual elevated levels of carbon monoxide. All measurements of toluene undertaken using sorbent tubes were well below the BS standard comfort limit of 153 mg m-3, the maximum concentration of toluene measured during flight being 0.17 mg m-3. In the absence of specific cabin air standards for the other pollutants measured in this study, reference is made to other standards and guidelines established, for example, for domestic (home) or occupational environments. Such standards/guidelines are available for TCE, TBP, TOCP, xylenes and limonene (as well as for toluene and CO). None of these standards/guidelines was exceeded. One short term (5 minute) concentration of limonene occurred (during Part 3 of the study) that exceeded a recommended long term exposure limit; however, this short duration peak would have a small impact on longer term average exposure. It is informative also to compare measured cabin air concentrations with levels typically seen in domestic indoor environments. Based on the reasonably extensive database for VOCs in indoor air in buildings, it can be concluded that the concentrations of toluene, limonene, xylenes, undecane and TCE in the aircraft cabin air are of similar magnitude to those occurring in homes in developed countries. Concentrations of CO generated by combustion sources, notably gas cookers, are often higher than those occurring in the aircraft cabins. For TBP and TCPs, there are few data to allow comparison of the measured levels in aircraft cabin air with the indoor air in buildings. There are more extensive data available on levels of organophosphates in household dust, including studies reporting levels of TBP, but these are of limited relevance to the present study. It is notable that in over 95% of the cabin air samples, no detectable amounts of TOCP or other TCPs were found. TBP was detected more routinely, but not in the majority of samples. The highest level of TBP recorded was 21.8 μg m-3 (overall mean 1.07 μg m-3) which exceeds any reported domestic indoor air level. TBP levels were highest during first engine start. Mean concentrations of most VOCs showed a trend, with minimum values occurring during the main phases of flight (climb to descent) and higher values when on the ground and during take-off. This trend was not found for limonene or the TOCP and other TCP measurements. Regarding the possible influence of aircraft type, no TCPs were detected during Part 3 (A320/1 aircraft), whereas limonene concentrations were relatively high on these flights. Other identified differences included highest concentrations of m+p-xylene occurring in Part 5 and lowest concentrations of toluene in Part 2. In conclusion, this study successfully completed a range of air quality measurements during the course of 100 flights. No fume events occurred during these flights that triggered the airline‟s protocols for formal reporting of incidents. Flight and cabin crew, as well as the investigating scientists reported a number of fume /smell events in a post-flight questionnaire. Samples specifically taken during recorded air quality events did not have notably elevated concentrations of any of the individually measured pollutants. Therefore, with respect to the conditions of flight that were experienced during this study, there was no evidence for target pollutants occurring in the cabin air at levels exceeding available health and safety standards and guidelines.
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The proportion of ortho tricresyl phosphate isomers is supposed to be a key determinant of the toxicity of jet oils. The precursor materials currently used in oil formulation are, therefore, chosen to have very low ortho contents. Nevertheless, recent measurements of tricresyl phosphates in cabin air during flight indicate a significant presence of ortho isomers. This suggests that isomerization to increase the ortho content is occurring during jet engine operation.
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Aircraft cabin air can possibly be contaminated by tricresyl phosphates (TCP) from jet engine oils during fume events. o-TCP, a known neurotoxin, has been addressed to be an agent that might cause the symptoms reported by cabin crews after fume events. A total of 332 urine samples of pilots and cabin crew members in common passenger airplanes, who reported fume/odour during their last flight, were analysed for three isomers of tricresyl phosphate metabolites as well as dialkyl and diaryl phosphate metabolites of four flame retardants. None of the samples contained o-TCP metabolites above the limit of detection (LOD 0.5 μg/l). Only one sample contained metabolites of m- and p-tricresyl phosphates with levels near the LOD. Median metabolite levels of tributyl phosphate (TBP), tris-(2-chloroethyl) phosphate (TCEP) and triphenyl phosphate (TPP) (DBP 0.28 μg/l; BCEP 0.33 μg/l; DPP 1.1 μg/l) were found to be significantly higher than in unexposed persons from the general population. Median tris-(2-chloropropyl) phosphate (TCPP) metabolite levels were significantly not higher in air crews than in controls. Health complaints reported by air crews can hardly be addressed to o-TCP exposure in cabin air. Elevated metabolite levels for TBP, TCEP and TPP in air crews might occur due to traces of hydraulic fluid in cabin air (TBP, TPP) or due to release of commonly used flame retardants from the highly flame protected environment in the airplane. A slight occupational exposure of air crews to organophosphates was shown.
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Organophosphorus (OP) nerve agents and pesticides inhibit acetylcholinesterase (AChE), and this is thought to be a primary mechanism mediating the neurotoxicity of these compounds. However, a number of observations suggest that mechanisms other than or in addition to AChE inhibition contribute to OP neurotoxicity. There is significant experimental evidence that acute OP intoxication elicits a robust inflammatory response, and emerging evidence suggests that chronic repeated low-level OP exposure also upregulates inflammatory mediators. A critical question that is just beginning to be addressed experimentally is the pathophysiologic relevance of inflammation in either acute or chronic OP intoxication. The goal of this article is to provide a brief review of the current status of our knowledge linking inflammation to OP intoxication, and to discuss the implications of these findings in the context of therapeutic and diagnostic approaches to OP neurotoxicity.
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The aircraft cabin and flight deck ventilation are supplied from partially compressed unfiltered bleed air directly from the engine. Worn or defective engine seals can result in the release of engine oil into the cabin air supply. Aircrew and passengers have complained of illness following such "fume events". Adverse health effects are hypothesized to result from exposure to tricresyl phosphate mixed esters, a chemical added to jet engine oil and hydraulic fluid for its anti-wear properties. Our goal was to develop a laboratory test for exposure to tricresyl phosphate. The assay was based on the fact that the active-site serine of butyrylcholinesterase reacts with the active metabolite of tri-o-cresyl phosphate, cresyl saligenin phosphate, to make a stable phosphorylated adduct with an added mass of 80 Da. No other organophosphorus agent makes this adduct in vivo on butyrylcholinesterase. Blood samples from jet airplane passengers were obtained 24-48 h after completing a flight. Butyrylcholinesterase was partially purified from 25 ml serum or plasma, digested with pepsin, enriched for phosphorylated peptides by binding to titanium oxide, and analyzed by mass spectrometry. Of 12 jet airplane passengers tested, 6 were positive for exposure to tri-o-cresyl phosphate that is, they had detectable amounts of the phosphorylated peptide FGEpSAGAAS. The level of exposure was very low. No more than 0.05 to 3% of plasma butyrylcholinesterase was modified. None of the subjects had toxic symptoms. Four of the positive subjects were retested 3 to 7 months following their last airplane trip and were found to be negative for phosphorylated butyrylcholinesterase. In conclusion, this is the first report of an assay that detects exposure to tri-o-cresyl phosphate in jet airplane travelers.
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Neurotoxicity of tricresyl phosphates (TCPs) and jet engine oil (JEO) containing TCPs were evaluated in studies conducted in both rat and hen. Results for currently produced samples ("conventional" and "low-toxicity") were compared with published findings on older samples to identify compositional changes and relate those changes to neurotoxic potential. Finally, a human risk assessment for exposure by oral ingestion of currently produced TCPs in JEO at 3% (JEO + 3%) was conducted. TCPs and certain other triaryl phosphates administered as single doses inhibited brain neuropathy target esterase (B-NTE; neurotoxic esterase) in the rat and the hen (hen 3.25 times as sensitive), and both species were deemed acceptable for initial screening purposes. Neither rat nor hen was sensitive enough to detect statistically significant inhibition of B-NTE after single doses of IEO + 3% "conventional" TCP. Subacute administration of 2 g/kg/d of JEO + 3% "conventional" TCP to the hen produced B-NTE inhibition (32%), which did not result in organophosphorus-induced delayed neurotoxicity (OPIDN). Subchronic administration of JEO + 3% TCP but not JEO + 1% TCP at 2 g/kg/d produced OPIDN. Thus, the threshold for OPIDN was between 20 and 60 mg "conventional" TCP/kg/d in JEO for 10 wk. The current "conventional" TCPs used in JEO and new "low-toxicity" TCPs now used in some JEO are synthesized from phenolic mixtures having reduced levels of ortho-cresol and ortho-xylenols resulting in TCPs of very high content of meta- and para-substituted phenyl moieties; this change in composition results in lower toxicity. The "conventional" TCPs still retain enough inhibitory activity to produce OPIDN, largely because of the presence of ortho-xylyl moieties; the "low-toxicity" TCPs are largely devoid of ortho substituents and have extremely low potential to cause OPIDN. The TCPs produced in the 1940s and 1950s were more than 400 times as toxic as the "low-toxicity" TCPs produced today. Analysis of the doses required to produce OPIDN in a subchronic hen study suggests that the minimum toxic dose of "conventional" TCP for producing OPIDN in a 70-kg person would be 280 mg/d, and for JEO containing 3% TCP, 9.4 g/d. Food products could be inadvertently contaminated with neat "conventional" TCP but it is unlikely that food such as cooking oil would be contaminated with enough JEO + 3% TCP to cause toxicity. Further, at the dosage required for neurotoxicity, it would be virtually impossible for a person to receive enough JEO + 3% TCP in the normal workplace (or in an aircraft) to cause such toxicity. There is no record of a JEO formulated with the modern "conventional" TCP causing human neurotoxicity.
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Jet oils are specialized synthetic oils used in high-performance jet engines. They have an appreciable hazard due to toxic ingredients, but are safe in use provided that maintenance personnel follow appropriate safety precautions and the oil stays in the engine. Aircraft engines that leak oil may expose others to the oils through uncontrolled exposure. Airplanes that use engines as a source of bleed air for cabin pressurization may have this source contaminated by the oil if an engine leaks. Examination of the ingredients of the oil indicates that at least two ingredients are hazardous: N-phenyl-1-naphthylamine (a skin sensitizer) and tricresyl phosphate (a neurotoxicant, if ortho-cresyl isomers are present). Publicly available information such as labels and MSDS understates the hazards of such ingredients and in the case of ortho-cresyl phosphates by several orders of magnitude.
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Tricresyl phosphate (TCP), and in particular its tri-ortho substituted isomer (o,o,o-TCP), has been frequently used in aircraft engine oil. Bleed air, provided to the flight deck and cabin can contain traces of TCP. TCP can cause neurotoxic effects in humans. Regularly, airline pilots complain about loss of memory, headaches, dizziness, tunnel vision and other neurotoxic effects. The concentrations of TCP reported in flight deck air (max. ca. 50-100ngm(-3) total TCP) do not exceed provisional toxicity thresholds. These thresholds, however, contain a very high uncertainty and need further underpinning. The many non-detects and relatively low TCP concentrations reported suggest that TCP on its own is not likely to be responsible for the reported health problems of pilots. Specific conditions in air planes and other toxic compounds present in bleed air, whether or not in combination with TCP, may be responsible for the reported neurotoxic syndromes. Sensitivity of individuals seems to be an important factor as well. The clinical signs observed with a selected group of pilots are serious enough to call for further elucidation of this issue.
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This study was conducted to determine the threshold concentration of tricresyl phosphate (TCP) in aviation engine oil able to cause delayed peripheral neuropathy in adult hens after repeated exposure. The study also evaluated the predictive value of endpoints usually used to measure acute peripheral neurotoxicity (neurotoxic esterase [NTE] inhibition, ataxia, and histopathologic changes), as measures of neurotoxicity in a subchronic study. Animals that received oil containing 3% TCP showed significant neurotoxicity that could not be accounted for by the small amount of TOCP present. Oil containing 1% TCP was without neurotoxic activity. There was an excellent correlation between percentage inhibition of NTE and development of neuropathy. An association was also seen for ataxia and neuropathology. Further study is needed to determine the phosphate ester isomers responsible for the significant neurotoxic potency demonstrated by the aviation engine oil containing 3% TCP.
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The cresol transformation was investigated on HZSM-5 at 380°C. Isomerization and disproportionation products were observed. Isomerization was the main reaction. The cresol isomerization rates on HZSM-5 increased fromortho- tometa- topara-isomer with decreasing molecular kinetic diameter. The initial conversion rates were in a ratiorp:rm:ro=20:3:1. The isomerization product selectivity favoured molecules with the smallest kinetic molecular diameter at the onset of the reaction, and as reaction proceeded, the reaction product composition was determined thermodynamically. Forortho-cresol, at low conversion them/pratio slightly decreased with conversion, and at higher conversions the selectivity became insensitive to the degree of conversion, giving am/pratio equal to 3. Formeta-cresol isomerization, thep/oratio decreased steadily with conversion, and the initialparaselectivity was associated to both transition state and product shape/size selectivity. The isomer equilibrium composition obtained was 36%ortho-, 48%meta-, and 16%para-cresol, in disagreement with the thermodynamically calculated composition. The isomerization rates were always greater than disproportionation rates. The isomerization rates followed the sequencerI(p)>rI(m)>rI(o), while the disproportionation rate sequence wasrD(p)>rD(m)≅rD(o). The initialI/Dselectivities were in a ratio (I/D)p:(I/D)m:(I/D)o=100:30:8.
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This descriptive study reports the results of assays performed to detect circulating autoantibodies in a panel of 7 proteins associated with the nervous system (NS) in sera of 12 healthy controls and a group of 34 flight crew members including both pilots and attendants who experienced adverse effects after exposure to air emissions sourced to the ventilation system in their aircrafts and subsequently sought medical attention. The proteins selected represent various types of proteins present in nerve cells that are affected by neuronal degeneration. In the sera samples from flight crew members and healthy controls, immunoglobin (IgG) was measured using Western blotting against neurofilament triplet proteins (NFP), tubulin, microtubule-associated tau proteins (tau), microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and glial S100B protein. Significant elevation in levels of circulating IgG-class autoantibodies in flight crew members was found. A symptom-free pilot was sampled before symptoms and then again afterward. This pilot developed clinical problems after flying for 45 h in 10 d. Significant increases in autoantibodies were noted to most of the tested proteins in the serum of this pilot after exposure to air emissions. The levels of autoantibodies rose with worsening of his condition compared to the serum sample collected prior to exposure. After cessation of flying for a year, this pilot's clinical condition improved, and eventually he recovered and his serum autoantibodies against nervous system proteins decreased. The case study with this pilot demonstrates a temporal relationship between exposure to air emissions, clinical condition, and level of serum autoantibodies to nervous system-specific proteins. Overall, these results suggest the possible development of neuronal injury and gliosis in flight crew members anecdotally exposed to cabin air emissions containing organophosphates. Thus, increased circulating serum autoantibodies resulting from neuronal damage may be used as biomarkers for chemical-induced CNS injury. The authors thank all of the participants who volunteered to take part in this case study. The technical work of Dr. Hagir B. Suliman and the art work of Sheref M. Abou-Donia are appreciated. This study was supported in part by the Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
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The problems of computing, storing, and retrieving precise masses of the many combinations of elements likely to occur in the mass spectra of organic compounds are considerable. They can be significantly reduced by the adoption of a mass scale in which the mass of the CH2 radical is taken as 14.0000 mass units. The advantage of this scale is that ions differing by one or more CH2 groups have the same mass defect. The precise masses of a series of alkyl naphthalene parent peaks, for example, are 127.9195, 141.9195, 155.9195, etc. Because of the identical mass defects, the similar origin of these peaks is recognizable without reference to tables of masses. Tables of the mass defects for combinations of H, C12, C13, N, O, S32, and S34 are presented.
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In a previous study on the pyridine ion (1) and the pyridine-2-ylid isomer (2), we reported that ions 2 readily react with H2O to produce 2-pyridone ions at m/z 95, by O-atom abstraction. The mechanism for this intriguing reaction, however, was not established. This prompted us to use model chemistry calculations (CBS-QB3) to probe various mechanistic scenarios and to perform complementary experiments with the new, more versatile, ion–molecule reaction chamber of the Mons Autospec 6F mass spectrometer. It appears that H2O is not reacting neutral that produces the 2-pyridone ion of the above reaction, but rather O2 from air co-introduced with the water vapour. Theory and experiment agree that the exothermic reaction of O2 with the pyridine-2-ylid ion leads to loss of 3O from a stable peroxide-type adduct ion at m/z 111. Similarly, pyridine-3-ylid ions (3) generate 3-pyridone ions, but the reaction in this case is thermoneutral. The m/z 111:95 peak intensity ratios in the spectra of the ion–molecule products from ions 2 and 3 may serve to differentiate the isomers.
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Industry, government, and labor representatives have all acknowledged that air supply sys-tems on commercial aircraft sometimes get contaminated with pyrolyzed engine oil or hydraulic fluid, but efforts to define "sometimes" have been lacking. Despite the lack of attention it has received, the answer to this "how often" question is important because it will influence the willingness of industry, as well as regulators and legislators, to develop and implement control measures to prevent such air supply contami-nation. To address this data gap, an industrial hygienist collected reports of air supply contamination over an 18-month period January 2006 through June 2007 from the following sources, all per defined inclusion criteria: 1 Service Difficulty Reports SDR and Accident and Incident Data System AIDS reports that airlines submitted to the Federal Aviation Administration FAA; 2 incidents that flight attendants docu-mented with one of 20 airlines and copied to one crewmember labor union; and 3 newspaper clips identified in online searches. A qualified airline mechanic reviewed each SDR and AIDS report with an oil or hydraulic fluid-related mechanical defect that did not explicitly mention oil or hydraulic fluid in combination with a specific word that indicated air supply contamination i.smoke" to determine its eligibility. The resulting dataset of 470 air supply contamination events reported in the U.S. commercial fleet over an 18-month period translates into an average of 0.86 events per day and includes 350 incidents reported by airlines to the FAA, 115 reported flight attendants to their airline, and 37 incidents reported by at least one newspaper. There was limited overlap between sources. The data are discussed in detail along with commentary on whether and how the data are representative, the health and operational costs associated with air supply contamination, and some preventive measures.
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Monitoring of tricresyl phosphate (TCP) contamination of cockpit air was undertaken in three types of military aircraft [fighter trainer (FT), fighter bomber (FB), and cargo transport (CT) aircraft]. The aircraft had a previous history of pilot complaints about cockpit air contamination suspected to originate from the engine bleed air supply through the entry of aircraft turbine engine oil (ATO) into the engine compressor. Air samples were collected in flight and on the ground during engine runs using sorbent tubes packed with Porapak Q and cellulose filters. A total of 78 air samples were analysed, from 46 different aircraft, and 48 samples were found to be below the limit of detection. Nine incidents of smoke/odour were identified during the study. The concentrations of toxic o-cresyl phosphate isomers were below the level of detection in all samples. The highest total TCP concentration was 51.3 μg m(-3), while most were generally found to be <5 μg m(-3) compared with the 8-h time-weighted average exposure limit of 100 μg m(-3) for tri-o-cresyl phosphate. The highest concentrations were found at high engine power. Although TCP contamination of cabin/cockpit air has been the subject of much concern in aviation, quantitative data are sparse.
Article
Synthetic polyol-based lubricating oils containing 3% of either commercial tricresyl phosphate (TCP), triphenylphosphorothionate (TPPT), or butylated triphenyl phosphate (BTP) additive were evaluated for neurotoxicity in the adult hen using clinical, biochemical, and neuropathological endpoints. Groups of 17-20 hens were administered the oils by oral gavage at a "limit dose" of 1 g/kg, 5 days a week for 13 weeks. A group of positive control hens was included which received 7.5 mg/kg of one isomer of TCP (tri-ortho-cresyl phosphate, TOCP) on the same regimen, with an additional oral dose of 500 mg/kg given 12 days before the end of the experiment. A negative control group received saline. Neurotoxic esterase (NTE) activity in brain and spinal cord of hens dosed with the lubricating oils was not significantly different from saline controls after 6 weeks of treatment. After 13 weeks of dosing, NTE was inhibited 23 to 34% in brains of lubricant-treated hens. Clinical assessments of walking ability did not indicate any differences between the negative control group and lubricant-treated hens. Moreover, neuropathological examination revealed no alterations indicative of organophosphorus-induced delayed neuropathy (OPIDN). In hens treated with the positive control, significant inhibition of NTE was observed in brain and spinal cord at both 6 and 13 weeks of dosing; this group also demonstrated clinical impairment and pathological lesions indicative of OPIDN. In conclusion, the results of the present study indicated that synthetic polyol-based lubricating oils containing up to 3% TCP, TPPT, or BTP had low neurotoxic potential and should not pose a hazard under realistic conditions of exposure.
Article
Commercial tricresyl phosphate (TCP) is a heterogeneous mixture of isomers and aryl phosphate congeners, known for many years to induce delayed neurotoxicity (OPIDN) in humans and experimental animals. In the past the isomer tri-o-cresyl phosphate (TOCP) was thought to be the component primarily responsible for OPIDN. It is now clear that other constituents, particularly the mono-o-esters, are not only neurotoxic but also may be more potent than pure TOCP. As a generality, the toxicity potential of a particular brand of TCP is related to its content of o-phenolic residues, whereby the maximal potential is reached when o-phenolics are 33% of the mix. Historically, human TCP toxicity has resulted from inadvertent or intentional contamination of foodstuffs or beverages. TCP products with high ortho-residues synthesized by older manufacturing methods were involved in most of these cases, and were likely much more neurotoxic milligram for milligram than TOCP. Because of the great variability of TCP products, there are no conventional workplace exposure standards. Based upon data from the hen and cat, estimated human safe exposure rates for pure TOCP are estimated to be 2.5 mg/kg for a single dose, and 0.13 mg/kg/d for repetitive exposures. These levels may also be applied to TCP when o-methyl-phenyl, o-ethyl-phenyl, and o-xylenyl components are appropriately limited during manufacture such that the TCP product is less neurotoxic than TOCP. There have been relatively few reports of toxicity associated with the manufacture or use of TCP in commerce and industry. Low vapor pressures of the constituents preclude the presence of significant quantities of TCP vapor in the atmosphere. A lubricant or other formulation containing TCP may appear in the air as a mist. By these criteria the U.S. Petroleum Oil Mist exposure standard is protective when the formulation contains 4% or less of low ortho-TCP. Exposure calculations indicate that estimated safe levels are not likely to be exceeded in the well-regulated workplace. If it is of short duration, even a heavy fog of oil particulate may not exceed the 8-h-average inhalation exposure standard. Modern manufacturing practices tend to minimize the ortho content and thus the toxicity of TCP. Because individual TCP brands and synthesis methods vary, manufacturers should be consulted concerning the properties of their individual products.
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At currently achievable Fourier transform ion cyclotron resonance broadband mass spectrometry resolving power (m/deltam50% > 350,000 for 200 < m/z < 1,000), it would be necessary to spread out a conventional mass spectrum over approximately 200 m in order to provide visual resolution of the most closely resolved peaks. Fortunately, there are natural gaps in a typical mass spectrum, spaced 1 Da apart, because virtually no commonly encountered elemental compositions yield masses at those values. Thus, it is possible to break a broadband mass spectrum into 1-Da segments, rotate each segment by 90 degrees, scale each segment according to its mass defect (i.e., difference between exact and nominal mass), and then compress the spacing between the segments to yield a compact display. For hydrocarbon systems, conversion from IUPAC mass to "Kendrick" mass (i.e., multiplying each mass by 14.00000/14.01565) further simplifies the display by rectilinearizing the peak patterns. The resulting display preserves not only the "coarse" spacings (e.g., approximately 1 Da between odd and even masses, corresponding to either even vs odd number of nitrogens or 12C(c) vs 12C(c-1)13C1 elemental compositions of the same molecule; approximately 2-Da separations, corresponding to a double bond or ring; approximately 14 Da separations, corresponding to one CH2 group) but also the "fine structure" (i.e., different mass defects for different elemental compositions) across each 1-Da segment. The method is illustrated for experimental electrospray ionization FTICR ultrahigh-resolution mass spectra of a petroleum crude oil. Several thousand elemental compositions may be resolved visually in a single one-page two-dimensional display, and various compound families-class (NnOoSs), type (Z in C(c)H2(c+z)NnOoSs), and alkylation series-may be identified visually as well.
Article
Paralysis in man and the domestic fowl caused by “ToCP” (tri-cresyl phosphate, tri-tolyl phosphate or TTP) is reviewed, and the search for a non-toxic plasticizer derived either from TTP or tri-xylenyl phosphate (tri-dimethylphenyl phosphate or TXP) is described. It had been previously shown that the ortho-tolyl esters are toxic but we found that their removal does not make the mixture non-toxic. The meta- and para-tolyl esters were known to be free from toxic effects and the 2: 4 and 2: 5 dimethylphenyl esters were equally shown to be non-toxic except in massive doses. We confirmed that the tri-ortho-ethylphenyl ester was non-toxic, but found the mono- and di-ortho-ethylphenyl phosphates to be highly toxic. We showed that TTP made from phenols with all the ortho-cresol and ortho-ethylphenol removed is non-toxic. With TXP, however, elimination of all ortho-cresol and ortho-ethylphenol from the raw materials does not result in a non-toxic plasticizer. Tri-ortho-n-propylphenyl phosphate was shown to non-toxic but esters containing one or two ortho-propylphenyl groups are toxic. The toxicity of the ortho-tolyl, ortho-ethylphenyl and ortho-propylphenyl groups is much reduced in the presence of the 3: 5-dimethylphenyl group. This influence is greatest in mono-ortho-propylphenyl-di-3: 5-dimethylphenyl phosphate which is non-toxic in five consecutive daily doses of 500 mg./kg. body weight. The removal of all ortho-cresol, ortho-ethylphenol and ortho-propylphenol from the raw material results in a non-toxic product which we termed non-toxic plasticizer “NTP”. This has been fed in various doses to a variety of mammals and a large number of chickens in short term tests without toxic effects. Our experiments showed that tri-meta-ethylphenyl phosphate is non-toxic but tri-para-ethylphenyl phosphate is highly toxic. The mixture from which NTP is made contains 10% of para-ethylphenol. Based on chemical statistics the tri-para-ethylphenyl ester can be present only in minute quantities, and we have shown that esters containing one or two para-ethylphenyl groups are non-toxic. An ester with a methyl group in the ortho, and an ethyl group in the para position in the same benzene nucleus (tri-2-methyl-4-ethylphenyl phosphate) we showed, surprisingly, to be non-toxic.
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