Peak AAA fatty acid homolog contaminants present in the dietary supplement l-Tryptophan associated with the onset of eosinophilia-myalgia syndrome. (15th September 2018)

• Record Type: Journal Article
• Authors: Klarskov, Klaus; Gagnon, Hugo; Racine, Mathieu; Boudreault, Pierre-Luc; Normandin, Chad; Marsault, Eric; Gleich, Gerald J.; Naylor, Stephen
• Is Part Of: Toxicology letters. Volume 294(2018)
• Page Start: 193
• Page End: 204
• Publication Date: 2018-09-15
• Subjects: AAA1-XXX all fatty acid homologs of AAA1 family -- AAA2-XXX all fatty acid homologs of AAA2 family -- CDC USA centers for disease control and prevention -- CE collision energy -- CES collision energy spread -- CID collision induced dissociation -- DoU degree(s) of unsaturation -- ESI electrospray ionization -- EMS eosinophilia-myalgia syndrome -- FDA USA food and drug administration -- HPLC high performance liquid chromatography -- IDA information-dependent acquisition -- LC–MS microcapillary HPLC-mass spectrometry -- LC-UV HPLC with UV detection -- L-Trp L-tryptophan -- MS/MS tandem mass spectrometry -- MSn multi-stage mass spectrometry -- NMR nuclear magnetic resonance -- O-PAP 1-Oleyl ester of PAP -- OO-PAP 1, 2-Di-Oleyl ester of PAP -- PAA 3-(phenylamino)alanine -- PAP 3-(phenylamino)-1, 2-propanediol -- SD showa denko K.K -- TOF time-of-flight -- TOS toxic oil syndrome; L-Tryptophan -- Eosinophilia-myalgia syndrome -- peak AAA -- Case-associated contaminants -- Dietary supplements -- Structural homologs -- Toxic oil syndrome; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2018.05.027
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Identification of eight new AAA fatty acid homologs inl -tryptophan. Homologs differ in terms of aliphatic chain length and isomeric structure. Quantification of AAA1 -343/AAA2 -343 and the eight homologs. Structural similarity of the AAA homologs to Toxic Oil case associated contaminants is discussed. Abstract: The eosinophilia-myalgia syndrome (EMS) outbreak that occurred in the USA and elsewhere in 1989 was caused by the ingestion of Showa Denko K.K. (SD) L -tryptophan (L-Trp). "Six compounds" detected in the L-Trp were reported as case-associated contaminants. Recently the final and most statistically significant contaminant, "Peak AAA" was structurally characterized. The "compound" was actually shown to be two structural isomers resulting from condensation reactions of L-Trp with fatty acids derived from the bacterial cell membrane. They were identified as the indole C-2 anteiso (AAA1 -343) and linear (AAA2 -343) aliphatic chain isomers. Based on those findings, we utilized a combination of on-line HPLC-electrospray ionization mass spectrometry (LC–MS), as well as both precursor and product ion tandem mass spectrometry (MS/MS) to facilitate identification of a homologous family of condensation products related to AAA1 -343 and AAA2 -343. We structurally characterized eight new AAA1 -XXX/AAA2 -XXX contaminants, where XXX represents the integer molecular ions of all the related homologs, differing by aliphatic chain length and isomer configuration. The contaminants were derived from the following fatty acids of the bacterial cell membrane, 5-methylheptanoic acid ( anteiso -C8:0) for AAA1 -315; n -octanoic acid ( n -C8:0) for AAA2 -315; 6-methyloctanoic acid ( anteiso -C9:0) for AAA1 -329; n -nonanoic acid (n-C9:0) for AAA2 -329; 10-methyldodecanoic acid ( anteiso -C13:0) for AAA1 -385; n -tridecanoic acid ( n -C13:0) for AAA2 -385; 11-methyltridecanoic acid ( anteiso -C14:0) for AAA1 -399; and n -tetradecanoic acid ( n -C14:0) for AAA2 -399. The concentration levels for these contaminants were estimated to be 0.1–7.9 μg / 500 mg of an individual SD L-Trp tablet or capsule The structural similarity of these homologs to case-related contaminants of Spanish Toxic Oil Syndrome (TOS) is discussed.