Sviluppo di tecniche di analisi ifenate per la quantificazione di biomarcatori di esposizione a tossici ambientali: gli acidi mercapturici

Indiveri, Paolo (2009) Sviluppo di tecniche di analisi ifenate per la quantificazione di biomarcatori di esposizione a tossici ambientali: gli acidi mercapturici , [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Sanità pubblica e medicina del lavoro, 21 Ciclo. DOI 10.6092/unibo/amsdottorato/1393.
Documenti full-text disponibili:
[img]
Anteprima
Documento PDF (Italiano) - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Download (3MB) | Anteprima

Abstract

Human biomonitoring (HBM) is an ideal tool for evaluating toxicant exposure in health risk assessment. Chemical substances or their metabolites related to environmental pollutants can be detected as biomarkers of exposure using a wide variety of biological fluids. Individual exposure to aromatic hydrocarbon compounds (benzene, toluene, and o-xylene –“BTX”) were analysed with a liquid chromatography coupled to electrospray ionisation-mass spectrometry (μHPLC-ESI-MS/MS) method for the simultaneous quantitative detection of the BTX exposure biomarker SPMA, SBMA and o-MBMA in human urine. Urinary S-phenylmercapturic acid (SPMA) is a biomarker proposed by the American Conference of Governmental Industrial Hygienists (ACGIH) for assessing occupational exposure to benzene (Biological Exposure Index of 25 microg/g creatinine). Urinary S-benzylmercapturic (SBMA) and o-methyl S-benzyl mercapturic acid (o-MBMA) are specific toluene and o-xylene metabolites of glutathione detoxicant pathways, proposed as reliable biomarkers of exposure. To this aim a pre-treatment of the urine with solid phase extraction (SPE) and an evaporation step were necessary to concentrate the mercapturic acids before instrumental analysis. A liquid chromatography separation was carried out with a reversed phase capillary column (Synergi 4u Max-RP) using a binary gradient composed of an acquous solution of formic acid 0.07% v/v and methanol. The mercapturic acids were determinated by negative-ion-mass spectrometry and the data were corrected using isotope-labelled analogs as internal standards. The analytical method follows U.S. Food and Drug Administration guidance and was applied to assess exposure to BTX in a group of 396 traffic wardens. The association between biomarker results and individual factors, such as age, sex and tobacco smoke were also investigated. The present work also included improvements in the methods used by modifying various chromatographic parameters and experimental procedures. A partial validation was conducted to evaluate LOD, precision, accuracy, recovery as well as matrix effects. Higher sensitivity will be possible in future biological monitoring programmes, allowing evaluation of very low level of BTX human exposure. Keywords: Human biomonitoring, aromatic hydrocarbons, biomarker of exposure, HPLC-MS/MS.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Indiveri, Paolo
Supervisore
Co-supervisore
Dottorato di ricerca
Scuola di dottorato
Scienze mediche e chirurgiche cliniche
Ciclo
21
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
monitoraggio biologico, idrocarburi aromatici, biomarcatori di esposizione, HPLC-MS-MS
URN:NBN
DOI
10.6092/unibo/amsdottorato/1393
Data di discussione
28 Aprile 2009
URI

Altri metadati

Statistica sui download

Gestione del documento: Visualizza la tesi

^