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Development, validation and characterization of an analytical method for the quantification of hydrolysable urinary metabolites and plasma protein adducts of 2,4-and 2,6-toluene diisocyanate, 1,5-naphthalene diisocyanate and 4,4 '-methylenediphenyl diisocyanate

Sennbro, Carl Johan LU ; Lindh, Christian LU ; Tinnerberg, Håkan LU ; Vidén, Cecilia LU ; Littorin, Margareta LU ; Welinder, Hans LU and Jönsson, Bo A LU (2003) In Biomarkers 8(3-4). p.204-217
Abstract
Occupational exposure to diisocyanates within the plastic industry causes irritation and disorders in the airway. The aim of this study was to develop, validate and characterize a method for the determination of 2,4-toluenediamine (2,4-TDA), 2,6-toluenediamine (2,6-TDA), 1,5-diaminonaphthalene (1,5-NDA) and 4,4'-methylenedianiline (4,4'-MDA) in hydrolysed urine and plasma, and to study the correlation between the plasma and urinary levels of these potential biomarkers of 2,4-toluene diisocyanate (2,4-TDI), 2,6-toluene diisocyanate (2,6-TDI), 1,5-naphthalene diisocyanate (1,5-NDI) and 4,4'-methylenediphenyl diisocyanate (4,4'-MDI), respectively. Samples were hydrolysed with 0.3 M NaOH at 100degreesC for 24 h. The diamines were extracted,... (More)
Occupational exposure to diisocyanates within the plastic industry causes irritation and disorders in the airway. The aim of this study was to develop, validate and characterize a method for the determination of 2,4-toluenediamine (2,4-TDA), 2,6-toluenediamine (2,6-TDA), 1,5-diaminonaphthalene (1,5-NDA) and 4,4'-methylenedianiline (4,4'-MDA) in hydrolysed urine and plasma, and to study the correlation between the plasma and urinary levels of these potential biomarkers of 2,4-toluene diisocyanate (2,4-TDI), 2,6-toluene diisocyanate (2,6-TDI), 1,5-naphthalene diisocyanate (1,5-NDI) and 4,4'-methylenediphenyl diisocyanate (4,4'-MDI), respectively. Samples were hydrolysed with 0.3 M NaOH at 100degreesC for 24 h. The diamines were extracted, derivatized with pentafluoropropionic acid anhydride, and quantified by selected ion monitoring on gas chromatography-mass spectrometry. The repeatability and reproducibility of the method were 7-18% and 7-19%, respectively. Dialysis experiments showed that the metabolites of 2,4-TDI, 2,6-TDI, 1,5-NDI and 4,4'-MDI in plasma were exclusively protein adducts. No free diamines were found in urine, indicating that all diisocyanate-related metabolites were in a conjugated form. For each diisocyanate-related biomarker, there were strongly significant correlations (p < 0.001) between individual levels of metabolites in plasma and urine, with Spearman's rank correlation coefficient (r(s)) values of 0.74-0.90. The methods presented here will be valuable for the development of biological monitoring methods for diisocyanates. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
diisocyanates, biological markers, gas chromatography-mass spectrometry, protein adducts
in
Biomarkers
volume
8
issue
3-4
pages
204 - 217
publisher
Taylor & Francis
external identifiers
  • wos:000184952000003
  • scopus:0141504136
ISSN
1366-5804
DOI
10.1080/1354750031000090660
language
English
LU publication?
yes
id
f48ca283-eef0-4aba-89ab-de0b4a9f708b (old id 303639)
date added to LUP
2007-09-21 12:31:59
date last changed
2018-02-11 03:29:27
@article{f48ca283-eef0-4aba-89ab-de0b4a9f708b,
  abstract     = {Occupational exposure to diisocyanates within the plastic industry causes irritation and disorders in the airway. The aim of this study was to develop, validate and characterize a method for the determination of 2,4-toluenediamine (2,4-TDA), 2,6-toluenediamine (2,6-TDA), 1,5-diaminonaphthalene (1,5-NDA) and 4,4'-methylenedianiline (4,4'-MDA) in hydrolysed urine and plasma, and to study the correlation between the plasma and urinary levels of these potential biomarkers of 2,4-toluene diisocyanate (2,4-TDI), 2,6-toluene diisocyanate (2,6-TDI), 1,5-naphthalene diisocyanate (1,5-NDI) and 4,4'-methylenediphenyl diisocyanate (4,4'-MDI), respectively. Samples were hydrolysed with 0.3 M NaOH at 100degreesC for 24 h. The diamines were extracted, derivatized with pentafluoropropionic acid anhydride, and quantified by selected ion monitoring on gas chromatography-mass spectrometry. The repeatability and reproducibility of the method were 7-18% and 7-19%, respectively. Dialysis experiments showed that the metabolites of 2,4-TDI, 2,6-TDI, 1,5-NDI and 4,4'-MDI in plasma were exclusively protein adducts. No free diamines were found in urine, indicating that all diisocyanate-related metabolites were in a conjugated form. For each diisocyanate-related biomarker, there were strongly significant correlations (p &lt; 0.001) between individual levels of metabolites in plasma and urine, with Spearman's rank correlation coefficient (r(s)) values of 0.74-0.90. The methods presented here will be valuable for the development of biological monitoring methods for diisocyanates.},
  author       = {Sennbro, Carl Johan and Lindh, Christian and Tinnerberg, Håkan and Vidén, Cecilia and Littorin, Margareta and Welinder, Hans and Jönsson, Bo A},
  issn         = {1366-5804},
  keyword      = {diisocyanates,biological markers,gas chromatography-mass spectrometry,protein adducts},
  language     = {eng},
  number       = {3-4},
  pages        = {204--217},
  publisher    = {Taylor & Francis},
  series       = {Biomarkers},
  title        = {Development, validation and characterization of an analytical method for the quantification of hydrolysable urinary metabolites and plasma protein adducts of 2,4-and 2,6-toluene diisocyanate, 1,5-naphthalene diisocyanate and 4,4 '-methylenediphenyl diisocyanate},
  url          = {http://dx.doi.org/10.1080/1354750031000090660},
  volume       = {8},
  year         = {2003},
}