Development of diagnostics in the search for an explanation of aerotoxic syndrome.
Aerotoxic syndrome is assumed to be caused by exposure to tricresyl phosphate, an additive in engine lubricants and hydraulic fluids that is activated to the toxic 2-(ortho-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (CBDP). Currently, there is no laboratory evidence to support intoxication of airline crew members by CBDP. Our goal was to develop methods for testing in vivo exposure by identifying and characterizing biomarkers. Mass spectrometry was used to study the reaction of CBDP with human albumin, free tyrosine, and human butyrylcholinesterase. Human albumin made a covalent bond with CBDP, adding a mass of 170amu to Tyr411 to yield the o-cresyl phosphotyrosine derivative. Human butyrylcholinesterase made a covalent bond with CBDP on Ser198 to yield five adducts with added masses of 80, 108, 156, 170, and 186amu. The most abundant adduct had an added mass of 80amu from phosphate (HPO(3)), a surprising result given that no pesticide or nerve agent is known to yield phosphorylated serine with an added mass of 80amu. The next most abundant adduct had an added mass of 170amu to form o-cresyl phosphoserine. It is concluded that toxic gases or oil mists in cabin air may form adducts on plasma butyrylcholinesterase and albumin, detectable by mass spectrometry.
Schopfer
Lawrence M
LM
Eppley Institute, University of Nebraska Medical Center, Omaha, 68198, USA. lmschopf@unmc.edu <lmschopf@unmc.edu>
Furlong
Clement E
CE
Lockridge
Oksana
O
D000393:Air Pollutants / Q000737:chemistry* / Q000633:toxicity; D000401:Aircraft; D015415:Biomarkers / Q000737:chemistry; D002091:Butyrylcholinesterase / Q000737:chemistry; D006801:Humans; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000633:toxicity; D012709:Serum Albumin / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014443:Tyrosine / Q000737:chemistry
D000393:Air Pollutants; D015415:Biomarkers; D009943:Organophosphorus Compounds; D012709:Serum Albumin; C000516:2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide; D014443:Tyrosine; D002091:Butyrylcholinesterase
Arch Environ Health. 2001 Mar-Apr;56(2):181-6
11339683
Klin Wochenschr. 1958 Jul 15;36(14):663-74
13576740
JAMA. 1982 Oct 15;248(15):1864-7
6750161
Lancet. 1959 Dec 5;2(7110):1019-21
13831987
Chem Res Toxicol. 2008 Sep;21(9):1787-94
18707141
Toxicol Sci. 2010 May;115(1):183-93
20142434
J Appl Toxicol. 2010 Aug;30(6):559-65
20809544
Biochem Pharmacol. 1961 Feb;5:332-42
13691286
Biochem Pharmacol. 1967 Feb;16(2):295-308
6029915
Nature. 1961 Sep 30;191:1396-7
13877086
Biochem Pharmacol. 1979;28(2):211-6
426836
Biochem J. 1957 Jun;66(2):237-42
13445678
J Chromatogr B Analyt Technol Biomed Life Sci. 2010 May 15;878(17-18):1297-311
19762289
Drug Metab Dispos. 2001 Sep;29(9):1201-4
11502728
Chem Res Toxicol. 2008 Feb;21(2):421-31
18163544
J Chromatogr A. 2008 Jul 25;1200(2):211-6
18550071
Toxicol Sci. 2010 Jul;116(1):23-31
20395308
J Med Chem Biol Radiol Def. 2005 Jul 1;3:nihms5095
16788731
Environ Res. 2002 Jun;89(2):146-64
12123648
Biochem Pharmacol. 1962 Apr-May;11:337-52
13890904
J Toxicol Clin Toxicol. 1995;33(4):373-4
7629908
Biochem J. 1954 Feb;56(2):185-9
13140171
Chem Res Toxicol. 2002 Apr;15(4):582-90
11952345
Chem Res Toxicol. 2004 Aug;17(8):983-98
15310231