Details:

Alternative Title:
Chem Res Toxicol
Personal Author:
Wisnewski, Adam V. ; Nassar, Ala F ; Liu, Jian ; Bello, Dhimiter ;
Wisnewski, Adam V. ; Nassar, Ala F ; Liu, Jian ; Bello, Dhimiter ; Less -
Description:
Biomonitoring of methylene diphenyl diisocyanate (MDI) in urine may be useful in industrial hygiene and exposure surveillance approaches toward disease (occupational asthma) prevention and in understanding pathways by which the internalized chemical is excreted. We explored possible urine biomarkers of MDI exposure in mice after respiratory tract exposure to MDI, as glutathione (GSH) reaction products (MDI-GSH), and after skin exposure to MDI dissolved in acetone. LC-MS analyses of urine identified a unique m/ z 543.29 [M + H]| ion from MDI-exposed mice but not from controls. The m/ z 543.29 [M + H]| ion was detectable within 24 h of a single MDI skin exposure and following multiple respiratory tract exposures to MDI-GSH reaction products. The m/ z 543.29 [M + H]| ion possessed properties of dilysine-MDI, including (a) an isotope distribution pattern for a molecule with the chemical formula C|H|N|O|, (b) the expected collision-induced dissociation (CID) fragmentation pattern upon MS/MS, and (c) a retention time in reversed-phase LC-MS identical to that of synthetic dilysine-MDI. Further MDI-specific Western blot studies suggested albumin (which contains multiple dilysine sites susceptible to MDI carbamylation) as a possible source for dilysine-MDI and the presence of MDI-conjugated albumin in urine up to 6 days after respiratory tract exposure. Two additional [M + H]| ions ( m/ z 558.17 and 863.23) were found exclusively in urine of mice exposed to MDI-GSH via the respiratory tract and possessed characteristics of previously described cyclized MDI-GSH and oxidized glutathione (GSSG)-MDI conjugates, respectively. Together the data identify urinary biomarkers of MDI exposure in mice and possible guidance for future translational investigation.
Subject:
[+]
Animals
Article
Biomarkers
Chromatography, Liquid
Dipeptides
Glutathione
Isocyanates
Mice
Molecular Structure
Skin
Tandem Mass Spectrometry

Source:
Chem Res Toxicol. 32(4):557-565 ;
Pubmed ID:
30724074
Pubmed Central ID:
PMC6465083
Document Type:
Journal Article ;
Funding:
R01 OH010941/OH/NIOSH CDC HHS/United States ; R01OH010941/ACL/ACL HHS/United States ;
R01 OH010941/OH/NIOSH CDC HHS/United States ; R01OH010941/ACL/ACL HHS/United States ; Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:74f8fc0d5e2798fe93fa3a70fd4c334a38a7494f023f7fd02d8753039ece85be
File Type:

Supporting Files

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