{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:20:05Z","timestamp":1790018405633,"version":"4.0.1"},"posted":{"date-parts":[[2025,4,19]]},"group-title":"Occupational and Environmental Health","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,19]],"date-time":"2025-04-19T00:00:00Z","timestamp":1745020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Most commercial passenger jet aircraft use compressed engine air after cooling as a source for ventilation and cabin pressurization onboard. This \u201cbleed air\u201d design means that engine oil and\/or hydraulic fluid can contaminate the ventilation supply air during otherwise normal flights, exposing onboard crewmembers and passengers to the fumes. The oils and hydraulic fluids contain a complex mixture of triaryl phosphates (TAPs) and decomposition products. Although the health and flight safety consequences of inhaling these fumes have been widely documented, measures of onboard inhalation exposure have been lacking. An approach is presented for documenting exposure to engine oil fumes by using high-resolution mass spectrometry (MS) to monitor and quantify post-translational modifications of subjects\u2019 butyrylcholinesterase (BChE) that are consistent with exposure to the engine oil TAPs. We hypothesized that plasma from exposed individuals would show modifications or adducts on the active site serine (Ser198) of BChE. Plasma BChE from 81 exposed subjects was purified to near homogeneity and concentrated using antibodies immobilized on paramagnetic beads. The purified BChE was eluted at low pH, neutralized, digested with trypsin, and analyzed by liquid chromatography (LC)-MS. In subjects reporting onboard oil fume exposures, the most consistent adduct modifying the Ser198-containing tryptic peptide had a mass value of +154.0031 Da. The normalized peak area (NPA) of the +154Da modification was determined by comparing the relative MS1 intensities of the +154Da-modified Ser198 containing peptide to the total observable peptides containing the active site, including missed cleavages. Notably, adducts from\n                  <jats:italic>in vitro<\/jats:italic>\n                  exposures of bioactivated TAPs to purified BChE conducted in this study (i.e., +80Da, +156Da, +170Da, and +186Da) as well as adducts reported in other earlier in vitro studies (i.e., +65Da, +80Da, +91Da, +107Da, +165Da, +180Da, +181Da, and +277Da) were not detected in exposed subjects. Of the 81 subjects in this study, the average NPA of +154Da-Ser198 resulted from fume event exposures that pre-dated 2013 (N=59); range = 0.46%-17.8%,\n                  <jats:italic>with X\u0305<\/jats:italic>\n                  =4.84% which was 9.7 times higher than control subjects (\n                  <jats:italic>X\u0305<\/jats:italic>\n                  = 0.50%) These data are uncorrected for the time lag between the reported exposure and the blood draw. Samples from the remaining 16 subjects with exposures from 2016-2024 showed only the 154Da modification at background levels (0.24%-1.13%;\n                  <jats:italic>X\u0305<\/jats:italic>\n                  =0.55%), as confirmed in control plasma samples from individuals who had not flown in at least three months. The observed reduction in the 154Da adduct over time in exposed individuals is likely a function of the change in the formulation of the OP blends added to engine oils during the course of the study. Further investigation into other protein biomarkers and adducts correlated with exposure to the current oil additives and hydraulic fluid fumes on aircraft is warranted. The most satisfactory solution would be to eliminate the exposure hazard by implementing bleed-free systems or, at a minimum, to develop less toxic oil formulations, suitable bleed air filters, and modified designs.\n                <\/jats:p>","DOI":"10.1101\/2025.04.17.25326021","type":"posted-content","created":{"date-parts":[[2025,4,20]],"date-time":"2025-04-20T02:05:21Z","timestamp":1745114721000},"source":"Crossref","is-referenced-by-count":2,"title":["Investigating biomarkers of exposure to jet aircraft oil fumes using mass spectrometry"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6489-7211","authenticated-orcid":false,"given":"Clement E.","family":"Furlong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Marsillach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Zelter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Rettie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana","family":"Lockridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Lundeen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Whittington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025062003150862000_2025.04.17.25326021v5.1","doi-asserted-by":"publisher","DOI":"10.1042\/bj0560185"},{"key":"2025062003150862000_2025.04.17.25326021v5.2","unstructured":"AFA, 2025. Summary of reportable chemicals listed on aviation engine oil and hydraulic fluid product Safety Data Sheets are reproduced by permission of the Air Safety, Health, and Security Department of the Association of Flight Attendants, AFL-CIO, Washington, DC. https:\/\/ashsd.afacwa.org."},{"key":"2025062003150862000_2025.04.17.25326021v5.3","doi-asserted-by":"publisher","DOI":"10.3390\/aerospace12050437"},{"key":"2025062003150862000_2025.04.17.25326021v5.4","doi-asserted-by":"publisher","DOI":"10.3390\/aerospace8050122"},{"key":"2025062003150862000_2025.04.17.25326021v5.5","unstructured":"ASHRAE. 2022. Research project 1830: Experimental characterization of aircraft bleed air particulate contamination. 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FAA-AM-83-12, Crane, CR ; Sanders, DC ; Endecott, BR ; et al. Federal Aviation Administration Civil Aeromedical Institute, Oklahoma City, OK. https:\/\/perma.cc\/V6CN-GCDU."},{"key":"2025062003150862000_2025.04.17.25326021v5.20","doi-asserted-by":"publisher","DOI":"10.1007\/BF01488746"},{"key":"2025062003150862000_2025.04.17.25326021v5.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0045-6535(99)00537-8"},{"key":"2025062003150862000_2025.04.17.25326021v5.22","unstructured":"Houtzager M , Noort D , Joosen M , Bos J , Jongeneel R , van Kesteren P , et al. 2017. Characterisation of the toxicity of aviation turbine engine oils after pyrolysis (AVOIL). 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