Biomarkers of Exposure to Pyrimethanil After Controlled Human Experiments
Faniband, Moosa LU ; Ekman, Eva LU ; Littorin, Margareta LU ; Maxe, Margareta LU ; Larsson, Estelle LU
and Lindh, Christian
LU
(2019)
In Journal of Analytical Toxicology
43(4).
p.277-283
- 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,... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/d0c72bd7-9929-4075-ac24-743dbbd73432
- author
- Faniband, Moosa
LU
; Ekman, Eva
LU
; Littorin, Margareta
LU
; Maxe, Margareta
LU
; Larsson, Estelle
LU
and Lindh, Christian
LU
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Analytical Toxicology
- volume
- 43
- issue
- 4
- pages
- 277 - 283
- publisher
- Oxford University Press
- external identifiers
-
- pmid:30462228
- scopus:85064821682
- ISSN
- 1945-2403
- DOI
- 10.1093/jat/bky091
- language
- English
- LU publication?
- yes
- id
- d0c72bd7-9929-4075-ac24-743dbbd73432
- date added to LUP
- 2018-11-28 12:35:17
- date last changed
- 2022-04-25 19:13:46
@article{d0c72bd7-9929-4075-ac24-743dbbd73432,
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.}},
author = {{Faniband, Moosa and Ekman, Eva and Littorin, Margareta and Maxe, Margareta and Larsson, Estelle and Lindh, Christian}},
issn = {{1945-2403}},
language = {{eng}},
number = {{4}},
pages = {{277--283}},
publisher = {{Oxford University Press}},
series = {{Journal of Analytical Toxicology}},
title = {{Biomarkers of Exposure to Pyrimethanil After Controlled Human Experiments}},
url = {{http://dx.doi.org/10.1093/jat/bky091}},
doi = {{10.1093/jat/bky091}},
volume = {{43}},
year = {{2019}},
}