| 1. |
- Faniband, Moosa
(författare)
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Human Exposure Biomarkers of Some Commonly Used Pesticides
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of pesticides has caused pollution of surface and groundwater, soil and air across the world. Many pesticides cause health effects in humans. General populations are exposed to some degree and diet is reported to be a main source of exposure. It is important to study exposure and exposure-effect relationships in occupational groups and in general populations. For such studies, good methods to monitor exposure, such as human biomonitoring are needed. However, for many pesticides, there is a lack of knowledge on exposure biomarkers and analytical methods to measure exposure. Thus, there is a need for validated biomarkers of exposure and analytical methods.In this thesis, new methods were developed and validated to analyze the fungicides thiabendazole (TBZ), imazalil (IMZ) and pyrimethanil (PYM) and their exposure biomarkers in urine using LC-MS/MS. Further, an LC-MS/MS method for analysis of glyphosate (GLY) and one of its metabolite in urine was established. The analytical methods were sensitive enough to measure a wide range of concentrations of exposure biomarkers in populations and showed good precisions.Human experimental exposures (oral and/or dermal) with TBZ, IMZ, PYM and GLY were performed with 2-3 volunteers to investigate basic toxicokinetics. The excretion of biomarkers in urine was rapid with short half-lives for all the four pesticides. The biomarkers of IMZ, TBZ and PYM were found conjugated with glucuronides and sulfates. The concentrations of biomarkers varied quantitatively with the degree of exposure.The analytical methods were applied to biomonitor the exposure in occupationally exposed groups and in general populations. The measured biomarkers in population groups in Sweden reflect concentrations which seem to be far below the excreted concentrations after an intake of a dose equivalent to a dose half or equal to the ADIs. The diet of the general population could be a possible source of exposure. The measured exposure biomarkers of IMZ in greenhouse workers and of PYM in orchardists were higher than the general population and reflected concentrations that were sometimes close to those following an exposure at a dose half or equal to the ADIs. In conclusion, the analytical methods performed well and can be applied in biomonitoring studies. The identified biomarkers of all four pesticides were related to the exposures and the human experiments facilitated validation of the biomarkers. The short urinary excretion half-lives require a well-planned sampling strategy.
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| 2. |
- Norén, Erika, et al.
(författare)
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Concentrations and temporal trends in pesticide biomarkers in urine of Swedish adolescents, 2000–2017
- 2020
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Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Springer Science and Business Media LLC. - 1559-0631 .- 1559-064X. ; 30:4, s. 756-767
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Tidskriftsartikel (refereegranskat)abstract
- Agricultural pesticides are extensively used for weed- and pest control, resulting in residues of these compounds in food. The general population is mainly exposed through dietary intake. Exposure to certain pesticides has been associated with adverse human health outcomes. Our aim was to assess urinary concentrations and temporal trends in the biomarkers of commonly used pesticides. Samples were collected from adolescents (n = 1060) in Scania, Sweden, from 2000 to 2017. Concentrations of 14 pesticide biomarkers were analyzed in urine using LC–MS/MS. Temporal trends in biomarker concentrations (ln-transformed) were evaluated using linear regression. Biomarkers of pyrethroids (3-PBA and DCCA), chlorpyrifos (TCPy), chlormequat (CCC), thiabendazole (OH-TBZ), and mancozeb (ETU) were detected in >90% of the population all sampling years. The biomarkers CCC and TCPy had the highest median concentrations (>0.8 µg/L), whereas the biomarkers of cyfluthrin (4F-3-PBA) and two pyrethroids (CFCA) had the lowest median concentrations (<0.02 µg/L). Increasing temporal trends were found for the biomarkers 3-PBA (3.7%/year), TCPy (1.7%/year) and biomarkers of pyrimethanil (11.9%/year) and tebuconazole (12.2%/year). Decreasing trends were found for CCC (–5.5%/year), OH-TBZ (−5.5%/year), and ETU (−3.9%/year). Our results suggest that Swedish adolescents are commonly exposed to pesticides in low concentrations (median concentrations <3.88 µg/L).
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| 3. |
- Tebby, Cleo, et al.
(författare)
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A generic PBTK model implemented in the MCRA platform : Predictive performance and uses in risk assessment of chemicals
- 2020
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- Physiologically-based toxicokinetic (PBTK) models are important tools for in vitro to in vivo or inter-species extrapolations in health risk assessment of foodborne and non-foodborne chemicals. Here we present a generic PBTK model implemented in the EuroMix toolbox, MCRA 9 and predict internal kinetics of nine chemicals (three endocrine disrupters, three liver steatosis inducers, and three developmental toxicants), in data-rich and data-poor conditions, when increasingly complex levels of parametrization are applied. At the first stage, only QSAR models were used to determine substance-specific parameters, then some parameter values were refined by estimates from substance-specific or high-throughput in vitro experiments. At the last stage, elimination or absorption parameters were calibrated based on available in vivo kinetic data. The results illustrate that parametrization plays a capital role in the output of the PBTK model, as it can change how chemicals are prioritized based on internal concentration factors. In data-poor situations, estimates can be far from observed values. In many cases of chronic exposure, the PBTK model can be summarized by an external to internal dose factor, and interspecies concentration factors can be used to perform interspecies extrapolation. We finally discuss the implementation and use of the model in the MCRA risk assessment platform.
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