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In the current paper we show that exposure of human callus to isocyanates leads to covalent modifications within keratin proteins. Mass spectrometric analyses of pronase digests of keratin isolated from exposed callus show that both mono- and di-adducts (for di-isocyanates) are predominantly formed on the ε-amino group of lysine. In addition, numerous modified tryptic keratin fragments were identified, demonstrating rather random lysine modification. Interestingly, preliminary experiments demonstrate that in case of MDI a similar lysine di-adduct was formed with lung elastin. Our data support the hypothesis that skin sensitization through antigenic modifications of skin proteins by isocyanates could play a role in occupational isocyanate-induced asthma. It is further envisaged that the elucidated adducts will also have great potential for use as biomarkers to assess skin exposure to isocyanates. Advantageously, the various lysine adducts display the presence of a characteristic daughter fragment at m/z 173.1 [lysine-NCO](+), enabling generic and rapid screening for exposure to isocyanates., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Organophosphate (OP) pesticides are neurotoxic compounds that are widely used in agriculture. Classical methods for monitoring OP exposure comprise the measurement of intact OP, its metabolites or cholinesterase activity. Newly developed methods focus on the analysis of the OP adduct bound to proteins such as butyrylcholinesterase (BuChE) and albumin. These adducts can be analyzed by means of fluoride reactivation or by analysis with LC-MS/MS of the pepsin or pronase digest of butyrylcholinesterase and albumin, respectively. The utility of these methods is illustrated through the analysis of plasma samples obtained from patients taken 1-49 days after ingestion of the organophosphate pesticides chlorpyrifos and/or diazinon. Thus, in this particular case several independent methodologies were applied to the biomedical samples, all pointing to the same exposure., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)