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
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/303639
- author
- Sennbro, Carl Johan LU ; Lindh, Christian LU ; Tinnerberg, Håkan LU ; Vidén, Cecilia LU ; Littorin, Margareta LU ; Welinder, Hans LU and Jönsson, Bo A LU
- organization
- publishing date
- 2003
- 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
- 2016-04-01 12:10:53
- date last changed
- 2022-04-21 03:36:50
@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 < 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}}, keywords = {{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}}, doi = {{10.1080/1354750031000090660}}, volume = {{8}}, year = {{2003}}, }