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Biomarkers of Exposure to Pyrimethanil After Controlled Human Experiments.
- Source :
-
Journal of analytical toxicology [J Anal Toxicol] 2019 May 01; Vol. 43 (4), pp. 277-283. - Publication Year :
- 2019
-
Abstract
- Pyrimethanil (PYM) is a fungicide used pre- and post-harvest on many crops. It has a low acute toxicity but is of toxicological concern because of its antiandrogenic properties. The aim of the current work was to investigate some metabolism and estimate elimination kinetics of PYM in humans after experimental oral and dermal exposure. A liquid chromatography triple quadrupole mass spectrometry (LC-MS-MS) method was developed and validated for the analysis of PYM and its metabolite 4-hydroxypyrimethanil (OH-PYM) in human urine. The method was applied to analyze urine obtained from two volunteers experimentally exposed to PYM. The elimination of OH-PYM seemed to follow first-order kinetics and a two-phase excretion. After the oral exposure, the elimination half-life of OH-PYM in the rapid phase was 5 and 3 h for the female and male volunteer, respectively. In the slower phase, it was 15 h in both volunteers. After the dermal exposure, the half-life in the rapid phase was 8 h in both volunteers. In the slower phase, it was 30 and 20 h, respectively. About 80% of the oral dose was recovered as urinary OH-PYM in both volunteers. The dermal dose recovered as urinary OH-PYM was 9.4% and 19%, in the female and male volunteer, respectively. OH-PYM was mainly found as a conjugate of sulfonate and glucuronic acid. No free PYM was found. The analytical method showed good within-run, between-run and between-batch precision with a coefficient of variation between 6% and 12%. A limit of detection of 0.1 ng/mL and a limit of quantification of 0.4 ng/mL were achieved for both the analytes. The method was applied to biomonitor PYM exposure in populations in Sweden. OH-PYM was detected in nearly 50% and 96% of samples from the environmentally and occupationally exposed populations, respectively.<br /> (© The Author(s) 2018. Published by Oxford University Press.)
- Subjects :
- Administration, Cutaneous
Administration, Oral
Adolescent
Adult
Aged
Aged, 80 and over
Androgen Antagonists administration & dosage
Chromatography, Liquid
Female
Fungicides, Industrial administration & dosage
Half-Life
Healthy Volunteers
Humans
Male
Middle Aged
Occupational Exposure
Pyrimidines administration & dosage
Sensitivity and Specificity
Sweden
Tandem Mass Spectrometry
Young Adult
Androgen Antagonists urine
Biomarkers urine
Environmental Monitoring methods
Fungicides, Industrial urine
Human Experimentation
Pyrimidines urine
Subjects
Details
- Language :
- English
- ISSN :
- 1945-2403
- Volume :
- 43
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of analytical toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 30462228
- Full Text :
- https://doi.org/10.1093/jat/bky091