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- Faniband, Moosa H., et al.
(författare)
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Human experimental exposure to glyphosate and biomonitoring of young Swedish adults
- 2021
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Ingår i: International Journal of Hygiene and Environmental Health. - : Elsevier BV. - 1438-4639. ; 231
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Tidskriftsartikel (refereegranskat)abstract
- Glyphosate (GLY), N-(phosphonomethyl) glycine, is the most widely used herbicide in the world. It is a broad-spectrum herbicide, also used in crop desiccation. Agricultural workers may be occupationally exposed and general populations may be exposed to GLY mainly through diet. We studied the kinetics of GLY by measuring the parent compound and its metabolite aminomethylphosphonic acid (AMPA) in urine samples of three volunteers after an experimental oral exposure. We further examined GLY exposure by measuring GLY and AMPA in spot urine samples of 197 young adults in the general population in Scania, southern Sweden. Urine samples were analyzed using LC-MS/MS. In the experimental exposure, three healthy volunteers received an oral dose equivalent to 50% of the ADI for GLY. Urinary samples were collected up to 100 h after the exposure. The excretion of GLY to urine seemed to follow first-order kinetics and a two-phase excretion. The excretion half-life of GLY (density adjusted) was 6–9 h in the rapid phase and 18–33 h in the slower phase. The total dose recovered as unchanged GLY in the urine samples of volunteers was 1–6%. The metabolite AMPA was found to be 0.01–0.04% of the total dose of GLY. In the population of young adults, the median concentration was below 0.1 μg/L and a maximum concentration being 3.39 μg/L (density adjusted). AMPA was generally detected in lower concentrations (maximum = 0.99 μg/L). A moderate correlation (Spearman's ρ = 0.56) was observed between GLY and AMPA concentrations. Overall, the results may suggest that GLY and AMPA partly originate from separate exposures and that unchanged GLY is a more suitable biomarker of exposure.
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| 2. |
- Liljedahl, Emelie Rietz, et al.
(författare)
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Filaggrin polymorphisms and the uptake of chemicals through the skin—a human experimental study
- 2021
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Ingår i: Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 129:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The filaggrin protein is important for skin barrier structure and function. Loss-of-function (null) mutations in the filaggrin gene FLG may increase dermal absorption of chemicals. OBJECTIVE: The objective of the study was to clarify if dermal absorption of chemicals differs depending on FLG genotype. METHOD: We performed a quantitative real-time polymerase chain reaction (qPCR)-based genetic screen for loss-of-function mutations (FLG null) in 432 volunteers from the general population in southern Sweden and identified 28 FLG null carriers. In a dermal exposure experiment, we exposed 23 FLG null and 31 wild-type (wt) carriers to three organic compounds common in the environment: the polycyclic aromatic hydrocarbon pyrene, the pesticide pyrimethanil, and the ultraviolet-light absorber oxybenzone. We then used liquid-chromatography mass-spectrometry to measure the concentrations of these chemicals or their metabolites in the subjects’ urine over 48 h following exposure. Furthermore, we used long-range PCR to measure FLG repeat copy number variants (CNV), and we performed population toxicokinetic analysis. RESULTS: Lag times for the uptake and dermal absorption rate of the chemicals differed significantly between FLG null and wt carriers with low (20–22 repeats) and high FLG CNV (23–24 repeats). We found a dose-dependent effect on chemical absorption with increasing lag times by increasing CNV for both pyrimethanil and pyrene, and decreasing area under the urinary excretion rate curve (AUCð0–40hÞ ) with increasing CNV for pyrimethanil. FLG null carriers excreted 18% and 110% more metabolite (estimated by AUCð0–40hÞ ) for pyrimethanil than wt carriers with low and high CNV, respectively. CONCLUSION: We conclude that FLG genotype influences the dermal absorption of some common chemicals. Overall, FLG null carriers were the most susceptible, with the shortest lag time and highest rate constants for skin absorption, and higher fractions of the applied dose excreted. Furthermore, our results indicate that low FLG CNV resulted in increased dermal absorption of chemicals. https://doi.org/10.1289/EHP7310.
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