Identification of Metabolites of the Fungicide Penconazole in Human Urine.
Penconazole (PEN) is a fungicide used in agriculture that has been classified as hazardous to humans and the environment. The objective of this work was to identify PEN urinary metabolites in humans and propose a biomarker for PEN exposure. Five urine samples were collected from agricultural workers who worked with and were exposed to PEN. Samples were analyzed by liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry, with the source operating in the electrospray ionization mode. Metabolites previously identified in animal studies were searched as possible metabolites in humans. Candidate metabolites were first identified by multiple reaction monitoring following the protonated molecular ions that generated the protonated triazole moiety, which is expected to be present in all PEN metabolites; second, the isotopic patterns of the molecular ions were checked for consistency with the presence of two chlorine atoms; third, the full mass spectra were evaluated for consistency with the molecular structure. Seven different oxidized metabolites were found, both in the free and glucuronide conjugate forms. The major metabolite was the monohydroxyl-derivative PEN-OH (median molar fraction approximately 0.92 as a sum of free and glucuronide conjugated form). The product of further oxidation was the carboxyl-derivate PEN-COOH (median molar fraction approximately 0.03). After hydrolysis with β-glucuronidase, the free compounds were quantified in the presence of deuterated PEN as an internal standard; PEN-OH levels ranged from 230 to 460 μg/L, and PEN-COOH levels ranged from 5.2 to 16.7 μg/L. We propose a pathway for PEN metabolism in humans and suggest PEN-OH, after hydrolysis of glucuronide conjugates, as a biomarker for monitoring human exposure to PEN.
Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
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Mercadante
Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
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Polledri
Sciex, Via Cappuccini 6, 20122 Milano, Italy.
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Scurati
Dipartimento di Scienze Biochimiche e Cliniche, Università degli Studi di Milano, and International Centre for Pesticides and Health Risks Protection (ICPS), ASST Fatebenefratelli Sacco, Ospedale "Luigi Sacco", Via GB Grassi 74, 20157 Milano, Italy.
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Moretto
Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
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Fustinoni
D002853:Chromatography, Liquid; D004781:Environmental Exposure; D005659:Fungicides, Industrial / Q000652:urine*; D006801:Humans; D057230:Limit of Detection; D013058:Mass Spectrometry; D014230:Triazoles / Q000652:urine*
D005659:Fungicides, Industrial; D014230:Triazoles; C087058:penconazole