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Vapor conjugation of toluene diisocyanate to specific lysines of human albumin.

Hettick JM; Siegel PD; Green BJ; Liu J; Wisnewski AV

Anal Biochem 2012 Feb; 421(2):706-711

https://doi.org/10.1016/j.ab.2011.12.013

20040181

Exposure to toluene diisocyanate (TDI), an industrially important crosslinking agent used in the production of polyurethane products, can cause asthma in sensitive workers. Albumin has been identified as a major reaction target for TDI in vivo, and TDI-albumin reaction products have been proposed to serve as exposure biomarkers and to act as asthmagens, yet they remain incompletely characterized. In the current study, we used a multiplexed tandem mass spectrometry (MS/MS) approach to identify the sites of albumin conjugation by TDI vapors, modeling the air/liquid interface of the lung. Vapor phase TDI was found to react with human albumin in a dose-dependent manner, with up to 18 potential sites of conjugation, the most susceptible being Lys351 and the dilysine site Lys413-414. Sites of vapor TDI conjugation to albumin were quantitatively limited compared with those recently described for liquid phase TDI, especially in domains IIA and IIIB of albumin. We hypothesize that the orientation of albumin at the air/liquid interface plays an important role in vapor TDI conjugation and, thus, could influence biological responses to exposure and the development of in vitro assays for exposure and immune sensitivity.

Toluenes; Polyurethane-foams; Biomarkers; Exposure-levels; Exposure-limits; Chemical-reactions; Chemical-composition; Mass-spectrometry; Vapors; Models; Lung; Lung-function; Lung-tissue; Lung-disorders; Humans; Men; Women; Immune-reaction; Immune-system; Immune-system-disorders; Immunologic-disorders; Author Keywords: Toluene diisocyanate; Human serum albumin; Tandem mass spectrometry; Allergy

Justin M. Hettick, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Morgantown, WV 26505

ANBCA2

584-84-9

20120215

Journal Article

jhettick@cdc.gov

2012

2

0003-2697

HELD

Manufacturing

Analytical Biochemistry

CT; WV